{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:58:39Z","timestamp":1788436719898,"version":"build-2803163510"},"reference-count":240,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T00:00:00Z","timestamp":1668470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health"},{"name":"National Cancer Institute"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Renal cell carcinoma is a heterogenous cancer composed of an increasing number of unique subtypes each with their own cellular and tumor behavior. The study of hereditary renal cell carcinoma, which composes just 5% of all types of tumor cases, has allowed for the elucidation of subtype-specific tumorigenesis mechanisms that can also be applied to their sporadic counterparts. This review will focus on the major forms of hereditary renal cell carcinoma and the genetic alterations contributing to their tumorigenesis, including von Hippel Lindau syndrome, Hereditary Papillary Renal Cell Carcinoma, Succinate Dehydrogenase-Deficient Renal Cell Carcinoma, Hereditary Leiomyomatosis and Renal Cell Carcinoma, BRCA Associated Protein 1 Tumor Predisposition Syndrome, Tuberous Sclerosis, Birt\u2013Hogg\u2013Dub\u00e9 Syndrome and Translocation RCC. The mechanisms for tumorigenesis described in this review are beginning to be exploited via the utilization of novel targets to treat renal cell carcinoma in a subtype-specific fashion.<\/jats:p>","DOI":"10.3390\/genes13112122","type":"journal-article","created":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T02:31:27Z","timestamp":1668565887000},"page":"2122","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Tumorigenesis Mechanisms Found in Hereditary Renal Cell Carcinoma: A Review"],"prefix":"10.3390","volume":"13","author":[{"given":"Bradley R.","family":"Webster","sequence":"first","affiliation":[{"name":"Center for Cancer Research, Urologic Oncology Branch, National Cancer Institute\/NIH, 10 Center Drive, CRC Room 2W-5940, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikhil","family":"Gopal","sequence":"additional","affiliation":[{"name":"Center for Cancer Research, Urologic Oncology Branch, National Cancer Institute\/NIH, 10 Center Drive, CRC Room 2W-5940, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1780-2627","authenticated-orcid":false,"given":"Mark W.","family":"Ball","sequence":"additional","affiliation":[{"name":"Center for Cancer Research, Urologic Oncology Branch, National Cancer Institute\/NIH, 10 Center Drive, CRC Room 2W-5940, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"871252","DOI":"10.3389\/fonc.2022.871252","article-title":"Models of Renal Cell Carcinoma Used to Investigate Molecular Mechanisms and Develop New Therapeutics","volume":"12","author":"Shapiro","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_2","first-page":"2022-vol3","article-title":"Renal cell carcinoma: An overview of the epidemiology, diagnosis, and treatment","volume":"39","author":"Bahadoram","year":"2022","journal-title":"G. Ital. Nefrol."},{"key":"ref_3","first-page":"4009","article-title":"Trichloroethylene Is Associated with Kidney Cancer Mortality: A Population-based Analysis","volume":"35","author":"Alanee","year":"2015","journal-title":"Anticancer Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1136\/oemed-2013-101443","article-title":"Arsenic in drinking water and renal cancers in rural Bangladesh","volume":"70","author":"Mostafa","year":"2013","journal-title":"Occup. Environ. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.urolonc.2011.10.001","article-title":"Environmental and modifiable risk factors in renal cell carcinoma","volume":"30","author":"Navai","year":"2012","journal-title":"Urol. Oncol."},{"key":"ref_6","first-page":"e1013","article-title":"Incidence, Mortality and Risk Factors of Kidney Cancer in the World","volume":"5","author":"Mahdavifar","year":"2018","journal-title":"World Cancer Res. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.eururo.2022.06.016","article-title":"The 2022 World Health Organization Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours","volume":"82","author":"Moch","year":"2022","journal-title":"Eur. Urol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/s41585-019-0211-5","article-title":"The Cancer Genome Atlas of renal cell carcinoma: Findings and clinical implications","volume":"16","author":"Linehan","year":"2019","journal-title":"Nat. Rev. Urol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1097\/MOU.0000000000000646","article-title":"Inherited kidney cancer syndromes","volume":"29","author":"Ball","year":"2019","journal-title":"Curr. Opin. Urol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1097\/CCO.0000000000000364","article-title":"Renal cell carcinoma: Molecular characterization and evolving treatment paradigms","volume":"29","author":"Ball","year":"2017","journal-title":"Curr. Opin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1001\/jama.1995.03520310062031","article-title":"Identification of the von Hippel-Lindau (VHL) gene. Its role in renal cancer","volume":"273","author":"Linehan","year":"1995","journal-title":"JAMA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1016\/0140-6736(91)91705-Y","article-title":"Clustering of features of von Hippel-Lindau syndrome: Evidence for a complex genetic locus","volume":"337","author":"Neumann","year":"1991","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e68","DOI":"10.1158\/1078-0432.CCR-17-0547","article-title":"Von Hippel-Lindau and Hereditary Pheochromocytoma\/Paraganglioma Syndromes: Clinical Features, Genetics, and Surveillance Recommendations in Childhood","volume":"23","author":"Rednam","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1126\/science.8493574","article-title":"Identification of the von Hippel-Lindau disease tumor suppressor gene","volume":"260","author":"Latif","year":"1993","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"20","DOI":"10.15586\/jkcvhl.2017.88","article-title":"A Review of Von Hippel-Lindau Syndrome","volume":"4","author":"Varshney","year":"2017","journal-title":"J. Kidney Cancer VHL"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1002\/humu.24194","article-title":"Comprehensive characterization of Alu-mediated breakpoints in germline VHL gene deletions and rearrangements in patients from 71 VHL families","volume":"42","author":"Vocke","year":"2021","journal-title":"Hum. Mutat."},{"key":"ref_17","first-page":"521","article-title":"Genetic analysis of von Hippel-Lindau disease","volume":"31","author":"Lolkema","year":"2010","journal-title":"Hum. Mutat."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5669","DOI":"10.2147\/OTT.S190753","article-title":"Von Hippel-Lindau Disease: Current Challenges and Future Prospects","volume":"13","author":"Glasker","year":"2020","journal-title":"Onco Targets Ther."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Testa, U., Pelosi, E., and Castelli, G. (2020). Genetic Alterations in Renal Cancers: Identification of The Mechanisms Underlying Cancer Initiation and Progression and of Therapeutic Targets. Medicines, 7.","DOI":"10.3390\/medicines7080044"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1136\/jmedgenet-2020-107308","article-title":"A germline 1;3 translocation disrupting the VHL gene: A novel genetic cause for von Hippel-Lindau","volume":"59","author":"Ricketts","year":"2020","journal-title":"J. Med. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"100922","DOI":"10.1016\/j.eucr.2019.100922","article-title":"Obstructive azoospermia secondary to bilateral epididymal cystadenomas in a patient with von Hippel-Lindau","volume":"27","author":"Gomella","year":"2019","journal-title":"Urol. Case Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1101\/gr.131110.111","article-title":"Genetic basis of kidney cancer: Role of genomics for the development of disease-based therapeutics","volume":"22","author":"Linehan","year":"2012","journal-title":"Genome Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1007\/s00345-020-03441-3","article-title":"Evaluation, diagnosis and surveillance of renal masses in the setting of VHL disease","volume":"39","author":"Chahoud","year":"2021","journal-title":"World, J. Urol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1136\/jmedgenet-2021-108216","article-title":"Clinical characteristics and risk factors for survival in affected offspring of von Hippel-Lindau disease patients","volume":"59","author":"Zhang","year":"2022","journal-title":"J. Med. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2010","DOI":"10.1016\/S0022-5347(01)66674-6","article-title":"Prevalence of microscopic lesions in grossly normal renal parenchyma from patients with von Hippel-Lindau disease, sporadic renal cell carcinoma and no renal disease: Clinical implications","volume":"154","author":"Walther","year":"1995","journal-title":"J. Urol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1007\/s11547-020-01310-y","article-title":"Relationship between visceral adipose tissue and genetic mutations (VHL and KDM5C) in clear cell renal cell carcinoma","volume":"126","author":"Greco","year":"2021","journal-title":"Radiol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1136\/jmg.33.4.328","article-title":"Phenotypic expression in von Hippel-Lindau disease: Correlations with germline VHL gene mutations","volume":"33","author":"Maher","year":"1996","journal-title":"J. Med. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1007\/s00345-018-2288-5","article-title":"Hereditary renal cell carcinoma syndromes: Diagnosis, surveillance and management","volume":"36","author":"Maher","year":"2018","journal-title":"World, J. Urol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1002\/humu.1380050109","article-title":"Germline mutations in the von Hippel-Lindau disease tumor suppressor gene: Correlations with phenotype","volume":"5","author":"Chen","year":"1995","journal-title":"Hum. Mutat."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/ejhg.2010.175","article-title":"von Hippel-Lindau disease: A clinical and scientific review","volume":"19","author":"Maher","year":"2011","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1038\/gim.2017.261","article-title":"Genotype and phenotype correlation in von Hippel-Lindau disease based on alteration of the HIF-alpha binding site in VHL protein","volume":"20","author":"Liu","year":"2018","journal-title":"Genet. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/s004390000265","article-title":"Genotype-phenotype correlations in families with deletions in the von Hippel-Lindau (VHL) gene","volume":"106","author":"Hes","year":"2000","journal-title":"Hum. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.urology.2020.02.015","article-title":"Long-term Functional and Oncologic Outcomes of Partial Adrenalectomy for Pheochromocytoma","volume":"140","author":"Gomella","year":"2020","journal-title":"Urology"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Sanford, T., Gomella, P.T., Siddiqui, R., Su, D., An, J.Y., Bratslavsky, G., Ball, M.W., Linehan, W.M., and Metwalli, A.R. (2021). Long term outcomes for patients with von Hippel-Lindau and Pheochromocytoma: Defining the role of active surveillance. Urol. Oncol., 39.","DOI":"10.1016\/j.urolonc.2020.11.019"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41525-022-00291-3","article-title":"VHL mosaicism: The added value of multi-tissue analysis","volume":"7","author":"Oldfield","year":"2022","journal-title":"NPJ Genom. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4674","DOI":"10.1158\/0008-5472.CAN-09-0146","article-title":"Patterns of gene expression and copy-number alterations in von-hippel lindau disease-associated and sporadic clear cell carcinoma of the kidney","volume":"69","author":"Beroukhim","year":"2009","journal-title":"Cancer Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1126\/science.7660122","article-title":"Inhibition of transcription elongation by the VHL tumor suppressor protein","volume":"269","author":"Duan","year":"1995","journal-title":"Science"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1126\/science.7660130","article-title":"Binding of the von Hippel-Lindau tumor suppressor protein to Elongin B and C","volume":"269","author":"Kibel","year":"1995","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1073\/pnas.94.6.2156","article-title":"The von Hippel-Lindau tumor-suppressor gene product forms a stable complex with human CUL-2, a member of the Cdc53 family of proteins","volume":"94","author":"Pause","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1126\/science.284.5414.657","article-title":"Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase","volume":"284","author":"Kamura","year":"1999","journal-title":"Science"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2728","DOI":"10.1093\/hmg\/ddac066","article-title":"Elongin C (ELOC\/TCEB1) associated von Hippel-Lindau disease","volume":"31","author":"Andreou","year":"2022","journal-title":"Hum. Mol. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/20459","article-title":"The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis","volume":"399","author":"Maxwell","year":"1999","journal-title":"Nature"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1126\/science.1059796","article-title":"Targeting of HIF-\u03b1 to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation","volume":"292","author":"Jaakkola","year":"2001","journal-title":"Science"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1126\/science.1059817","article-title":"HIF\u03b1 targeted for VHL-mediated destruction by proline hydroxylation: Implications for O2 sensing","volume":"292","author":"Ivan","year":"2001","journal-title":"Science"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4555","DOI":"10.1200\/JCO.2021.39.15_suppl.4555","article-title":"Phase 2 study of belzutifan (MK-6482), an oral hypoxia-inducible factor 2\u03b1 (HIF-2\u03b1) inhibitor, for Von Hippel-Lindau (VHL) disease-associated clear cell renal cell carcinoma (ccRCC)","volume":"39","author":"Srinivasan","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.molcel.2010.09.022","article-title":"Hypoxia-inducible factors and the response to hypoxic stress","volume":"40","author":"Majmundar","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.semcancer.2012.06.001","article-title":"The VHL\/HIF axis in clear cell renal carcinoma","volume":"23","author":"Shen","year":"2013","journal-title":"Semin. Cancer Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1038\/nrc1187","article-title":"Targeting HIF-1 for cancer therapy","volume":"3","author":"Semenza","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1038\/s41467-017-01965-8","article-title":"HIF drives lipid deposition and cancer in ccRCC via repression of fatty acid metabolism","volume":"8","author":"Du","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1038\/sj.bjc.6601657","article-title":"Gene array of VHL mutation and hypoxia shows novel hypoxia-induced genes and that cyclin D1 is a VHL target gene","volume":"90","author":"Wykoff","year":"2004","journal-title":"Br. J. Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e31","DOI":"10.1097\/JU.0000000000002516.06","article-title":"PD01\u201306 GCN5L1 regulates mitochondrial acetylation, lipid accumulation and cell growth in vhl-deficient clear cell renal cell carcinoma","volume":"207","author":"Webster","year":"2022","journal-title":"J. Urol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/s42255-022-00593-x","article-title":"Impaired oxygen-sensitive regulation of mitochondrial biogenesis within the von Hippel-Lindau syndrome","volume":"4","author":"Li","year":"2022","journal-title":"Nat. Metab."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"104538","DOI":"10.1016\/j.ejmg.2022.104538","article-title":"von Hippel-Lindau disease: Updated guideline for diagnosis and surveillance","volume":"65","author":"Louise","year":"2022","journal-title":"Eur. J. Med. Genet."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1007\/BF00182972","article-title":"Enucleation procedures in patients with multiple hereditary renal tumors","volume":"13","author":"Walther","year":"1995","journal-title":"World, J. Urol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.urology.2021.03.032","article-title":"X-Capsular Incision for Tumor Enucleation (X-CITE)-Technique: A Method to Maximize Renal Parenchymal Preservation for Completely Endophytic Renal Tumors","volume":"154","author":"Lebastchi","year":"2021","journal-title":"Urology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1016\/j.juro.2009.06.036","article-title":"Robot assisted partial nephrectomy for multiple renal masses: Feasibility and results of initial experience","volume":"182","author":"Boris","year":"2009","journal-title":"J. Urol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.juro.2007.08.150","article-title":"Salvage partial nephrectomy for hereditary renal cancer: Feasibility and outcomes","volume":"179","author":"Bratslavsky","year":"2008","journal-title":"J. Urol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Baiocco, J.A., Ball, M.W., Pappajohn, A.K., Rayn, K.N., Bratslavsky, G., Boyle, S.L., Linehan, W.M., and Metwalli, A.R. (2019). A comparison of outcomes for standard and multiplex partial nephrectomy in a solitary kidney: The National Cancer Institute experience. Urol. Oncol., 37.","DOI":"10.1016\/j.urolonc.2019.02.015"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"244","DOI":"10.3389\/fonc.2017.00244","article-title":"Multiplex partial nephrectomy, repeat partial nephrectomy, and salvage partial nephrectomy remain the primary treatment in multifocal and hereditary kidney cancer","volume":"7","author":"Baiocco","year":"2017","journal-title":"Front. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1089\/end.2016.0517","article-title":"Repeat robotic partial nephrectomy: Characteristics, complications, and renal functional outcomes","volume":"30","author":"Watson","year":"2016","journal-title":"J. Endourol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1097\/JU.0000000000001837","article-title":"Reoperative Partial Nephrectomy-Does Previous Surgical Footprint Impact Outcomes?","volume":"206","author":"Gurram","year":"2021","journal-title":"J. Urol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1016\/S0022-5347(05)68930-6","article-title":"Renal cancer in families with hereditary renal cancer: Prospective analysis of a tumor size threshold for renal parenchymal sparing surgery","volume":"161","author":"Walther","year":"1999","journal-title":"J. Urol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1200\/JCO.19.02263","article-title":"Growth Rates of Genetically Defined Renal Tumors: Implications for Active Surveillance and Intervention","volume":"38","author":"Ball","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3554","DOI":"10.1007\/s00261-022-03610-5","article-title":"An MRI-based radiomics model to predict clear cell renal cell carcinoma growth rate classes in patients with von Hippel-Lindau syndrome","volume":"47","author":"Anari","year":"2022","journal-title":"Abdom. Radiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1097\/MNM.0000000000001251","article-title":"Role of [68Ga]DOTANOC PET\/computed tomography and [131I]MIBG scintigraphy in the management of patients with pheochromocytoma and paraganglioma: A prospective study","volume":"41","author":"Singh","year":"2020","journal-title":"Nucl. Med. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1177\/1758834010361470","article-title":"Updates on novel therapies for metastatic renal cell carcinoma","volume":"2","author":"Courtney","year":"2010","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"71","DOI":"10.6004\/jnccn.2022.0001","article-title":"Kidney Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology","volume":"20","author":"Motzer","year":"2022","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2957","DOI":"10.1200\/JCO.22.00868","article-title":"Management of Metastatic Clear Cell Renal Cell Carcinoma: ASCO Guideline","volume":"40","author":"Rathmell","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1056\/NEJMoa2103425","article-title":"Belzutifan for Renal Cell Carcinoma in von Hippel\u2013Lindau Disease","volume":"385","author":"Jonasch","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"v356","DOI":"10.1093\/annonc\/mdz249.010","article-title":"A first-in-human phase I\/II trial of the oral HIF-2a inhibitor PT2977 in patients with advanced RCC","volume":"30","author":"Jonasch","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Fallah, J., Brave, M.H., Weinstock, C., Mehta, G.U., Bradford, D., Gittleman, H., Bloomquist, E.W., Charlab, R., Hamed, S.S., and Miller, C.P. (2022). FDA Approval Summary: Belzutifan for von Hippel-Lindau disease associated tumors. Clin. Cancer Res.","DOI":"10.1158\/1078-0432.CCR-22-1054"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/ng0597-68","article-title":"Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas","volume":"16","author":"Schmidt","year":"1997","journal-title":"Nat. Genet."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Marona, P., Gorka, J., Kotlinowski, J., Majka, M., Jura, J., and Miekus, K. (2019). C-Met as a Key Factor Responsible for Sustaining Undifferentiated Phenotype and Therapy Resistance in Renal Carcinomas. Cells, 8.","DOI":"10.3390\/cells8030272"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"S21","DOI":"10.1177\/1758834011422557","article-title":"c-MET as a potential therapeutic target and biomarker in cancer","volume":"3","author":"Sierra","year":"2011","journal-title":"Adv. Med. Oncol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/S0022-5347(01)67601-8","article-title":"Hereditary papillary renal cell carcinoma: Clinical studies in 10 families","volume":"153","author":"Zbar","year":"1995","journal-title":"J. Urol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/S0022-5347(17)35015-2","article-title":"Hereditary papillary renal cell carcinoma","volume":"151","author":"Zbar","year":"1994","journal-title":"J. Urol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1097\/01.ju.0000139583.63354.e0","article-title":"Early onset hereditary papillary renal carcinoma: Germline missense mutations in the tyrosine kinase domain of the met proto-oncogene","volume":"172","author":"Schmidt","year":"2004","journal-title":"J. Urol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1002\/humu.24313","article-title":"Novel germline MET pathogenic variants in French patients with papillary renal cell carcinomas type I","volume":"43","author":"Sebai","year":"2022","journal-title":"Hum. Mutat."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S0022-5347(05)64830-6","article-title":"Biological significance of c-met over expression in papillary renal cell carcinoma","volume":"168","author":"Sweeney","year":"2002","journal-title":"J. Urol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1056\/NEJMoa1505917","article-title":"Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma","volume":"374","author":"Linehan","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1002\/gcc.22940","article-title":"Characterization of genetically defined sporadic and hereditary type 1 papillary renal cell carcinoma cell lines","volume":"60","author":"Yang","year":"2021","journal-title":"Genes Chromosom. Cancer"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.18632\/oncotarget.13540","article-title":"MET expression and copy number status in clear-cell renal cell carcinoma: Prognostic value and potential predictive marker","volume":"8","author":"Keith","year":"2017","journal-title":"Oncotarget"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1097\/00004728-199709000-00014","article-title":"Imaging features of hereditary papillary renal cancers","volume":"21","author":"Choyke","year":"1997","journal-title":"J. Comput. Assist. Tomogr."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.1158\/1078-0432.CCR-12-2791","article-title":"Targeting the HGF\/c-MET pathway in hepatocellular carcinoma","volume":"19","author":"Goyal","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"535","DOI":"10.3892\/ijo.2012.1728","article-title":"HGF regulates VEGF expression via the c-Met receptor downstream pathways, PI3K\/Akt, MAPK and STAT3, in CT26 murine cells","volume":"42","author":"Matsumura","year":"2013","journal-title":"Int. J. Oncol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3699","DOI":"10.1158\/0008-5472.CAN-05-0617","article-title":"Inactivation of von Hippel-Lindau gene induces constitutive phosphorylation of MET protein in clear cell renal carcinoma","volume":"66","author":"Nakaigawa","year":"2006","journal-title":"Cancer Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"4905","DOI":"10.1158\/0008-5472.CAN-16-3190","article-title":"MCPIP1 Downregulation in Clear Cell Renal Cell Carcinoma Promotes Vascularization and Metastatic Progression","volume":"77","author":"Marona","year":"2017","journal-title":"Cancer Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/S0022-5347(05)67893-7","article-title":"Prevalence of microscopic tumors in normal appearing renal parenchyma of patients with hereditary papillary renal cancer","volume":"163","author":"Ornstein","year":"2000","journal-title":"J. Urol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1097\/MOU.0000000000000094","article-title":"Nephron-sparing surgery for multifocal and hereditary renal tumors","volume":"24","author":"Metwalli","year":"2014","journal-title":"Curr. Opin. Urol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/S0022-5347(05)66524-X","article-title":"Parenchymal sparing surgery in patients with hereditary renal cell carcinoma: 10-year experience","volume":"165","author":"Herring","year":"2001","journal-title":"J. Urol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.ejca.2018.08.014","article-title":"Cabozantinib for the treatment of patients with metastatic non-clear cell renal cell carcinoma: A retrospective analysis","volume":"104","author":"Campbell","year":"2018","journal-title":"Eur. J. Cancer"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1001\/jamaoncol.2020.2218","article-title":"Efficacy of Savolitinib vs Sunitinib in Patients With MET-Driven Papillary Renal Cell Carcinoma: The SAVOIR Phase 3 Randomized Clinical Trial","volume":"6","author":"Choueiri","year":"2020","journal-title":"JAMA Oncol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.1200\/JCO.2017.72.2967","article-title":"Biomarker-Based Phase II Trial of Savolitinib in Patients With Advanced Papillary Renal Cell Cancer","volume":"35","author":"Choueiri","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1200\/JCO.2012.43.3383","article-title":"Phase II and biomarker study of the dual MET\/VEGFR2 inhibitor foretinib in patients with papillary renal cell carcinoma","volume":"31","author":"Choueiri","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.ejca.2017.10.014","article-title":"Crizotinib achieves long-lasting disease control in advanced papillary renal-cell carcinoma type 1 patients with MET mutations or amplification. EORTC 90101 CREATE trial","volume":"87","author":"Schoffski","year":"2017","journal-title":"Eur. J. Cancer"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"3596","DOI":"10.7150\/jca.35738","article-title":"Determination of the Expression of PD-L1 in the Morphologic Spectrum of Renal Cell Carcinoma","volume":"11","author":"Walter","year":"2020","journal-title":"J. Cancer"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"5034","DOI":"10.1200\/JCO.2020.38.15_suppl.5034","article-title":"First-line pembrolizumab (pembro) monotherapy for advanced nonclear cell renal cell carcinoma (nccRCC): Results from KEYNOTE-427 cohort B","volume":"38","author":"Walter","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1200\/JCO.2019.37.7_suppl.545","article-title":"A phase II study investigating the safety and efficacy of savolitinib and durvalumab in metastatic papillary renal cancer (CALYPSO)","volume":"37","author":"Powles","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.eururo.2016.02.029","article-title":"The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours","volume":"70","author":"Moch","year":"2016","journal-title":"Eur. Urol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1086\/381054","article-title":"Early-onset renal cell carcinoma as a novel extraparaganglial component of SDHB-associated heritable paraganglioma","volume":"74","author":"Vanharanta","year":"2004","journal-title":"Am. J. Hum. Genet."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1097\/PAT.0b013e3283539932","article-title":"Succinate dehydrogenase (SDH) and mitochondrial driven neoplasia","volume":"44","author":"Gill","year":"2012","journal-title":"Pathology"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1016\/j.juro.2012.08.030","article-title":"Succinate dehydrogenase kidney cancer: An aggressive example of the Warburg effect in cancer","volume":"188","author":"Ricketts","year":"2012","journal-title":"J. Urol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/s41581-019-0210-z","article-title":"Oncometabolites in renal cancer","volume":"16","author":"Yong","year":"2020","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"925582","DOI":"10.3389\/fonc.2022.925582","article-title":"Co-occurrence of VHL and SDHA Pathogenic Variants: A Case Report","volume":"12","author":"Tung","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1016\/j.bbabio.2011.07.003","article-title":"SDH mutations in cancer","volume":"1807","author":"Bardella","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_106","first-page":"689","article-title":"Germline SDHC mutation presenting as recurrent SDH deficient GIST and renal carcinoma","volume":"45","author":"Gill","year":"2013","journal-title":"Pathol.-J. RCPA"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"E1103","DOI":"10.1210\/jc.2013-1400","article-title":"Familial SDHA mutation associated with pituitary adenoma and pheochromocytoma\/paraganglioma","volume":"98","author":"Dwight","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1097\/PAS.0b013e3182260752","article-title":"Succinate dehydrogenase deficient GISTs: A clinicopathologic, immunohistochemical, and molecular genetic study of 66 gastric gists with predilection to young age","volume":"35","author":"Miettinen","year":"2011","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e04605","DOI":"10.1002\/ccr3.4605","article-title":"SDH-deficient renal cell carcinoma: A case report associated with a novel germline mutation","volume":"9","author":"Milionis","year":"2021","journal-title":"Clin. Case Rep."},{"key":"ref_110","first-page":"1403","article-title":"Clinicopathologic features of succinate dehydrogenase deficiencient renal cell carcinoma","volume":"13","author":"Zhu","year":"2020","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Kumar, R., Bonert, M., Naqvi, A., Zbuk, K., and Kapoor, A. (2018). SDH-deficient renal cell carcinoma\u2014Clinical, pathologic and genetic correlates: A case report. BMC Urol., 18.","DOI":"10.1186\/s12894-018-0422-8"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1038\/s41379-021-00998-1","article-title":"Expanding the clinicopathological spectrum of succinate dehydrogenase-deficient renal cell carcinoma with a focus on variant morphologies: A study of 62 new tumors in 59 patients","volume":"35","author":"Fuchs","year":"2021","journal-title":"Mod. Pathol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1097\/PAS.0000000000000292","article-title":"Succinate dehydrogenase (SDH)-deficient renal carcinoma: A morphologically distinct entity: A clinicopathologic series of 36 tumors from 27 patients","volume":"38","author":"Gill","year":"2014","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"100773","DOI":"10.1016\/j.currproblcancer.2021.100773","article-title":"Kidney cancer: From genes to therapy","volume":"45","author":"Webster","year":"2021","journal-title":"Curr. Probl. Cancer"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e2106947118","DOI":"10.1073\/pnas.2106947118","article-title":"Functional succinate dehydrogenase deficiency is a common adverse feature of clear cell renal cancer","volume":"118","author":"Aggarwal","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.ccr.2004.11.022","article-title":"Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase","volume":"7","author":"Selak","year":"2005","journal-title":"Cancer Cell"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/S0006-2952(02)01168-1","article-title":"Signal transduction to hypoxia-inducible factor 1","volume":"64","author":"Semenza","year":"2002","journal-title":"Biochem. Pharmacol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"23757","DOI":"10.1016\/S0021-9258(17)31580-6","article-title":"Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1","volume":"269","author":"Semenza","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.tibs.2017.01.003","article-title":"Mitochondrial Complex II: At the Crossroads","volume":"42","author":"Rohlena","year":"2017","journal-title":"Trends Biochem. Sci."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"100053","DOI":"10.1074\/mcp.RA120.002150","article-title":"Systematic Proteome and Lysine Succinylome Analysis Reveals Enhanced Cell Migration by Hyposuccinylation in Esophageal Squamous Cell Carcinoma","volume":"20","author":"Guo","year":"2021","journal-title":"Mol. Cell Proteom."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"622198","DOI":"10.3389\/fcell.2021.622198","article-title":"Succinylation Regulators Promote Clear Cell Renal Cell Carcinoma by Immune Regulation and RNA N6-Methyladenosine Methylation","volume":"9","author":"Lu","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.freeradbiomed.2019.01.030","article-title":"SIRT5-mediated SDHA desuccinylation promotes clear cell renal cell carcinoma tumorigenesis","volume":"134","author":"Ma","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1186\/s12967-021-03178-6","article-title":"SIRT5 functions as a tumor suppressor in renal cell carcinoma by reversing the Warburg effect","volume":"19","author":"Liu","year":"2021","journal-title":"J. Transl. Med."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"11187","DOI":"10.1080\/21655979.2022.2062537","article-title":"Functional deficiency of succinate dehydrogenase promotes tumorigenesis and development of clear cell renal cell carcinoma through weakening of ferroptosis","volume":"13","author":"Yang","year":"2022","journal-title":"Bioengineered"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1038\/s41586-020-2363-0","article-title":"Oncometabolites suppress DNA repair by disrupting local chromatin signalling","volume":"582","author":"Sulkowski","year":"2020","journal-title":"Nature"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1016\/j.eururo.2019.06.015","article-title":"Familial kidney cancer: Implications of new syndromes and molecular insights","volume":"76","author":"Carlo","year":"2019","journal-title":"Eur. Urol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"409","DOI":"10.2340\/0001555553409416","article-title":"Cutaneous leiomyomata with uterine leiomyomata","volume":"53","author":"Reed","year":"1973","journal-title":"Acta Derm. Venereol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"3387","DOI":"10.1073\/pnas.051633798","article-title":"Inherited susceptibility to uterine leiomyomas and renal cell cancer","volume":"98","author":"Launonen","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1097\/PAS.0b013e31804375b8","article-title":"The morphologic spectrum of kidney tumors in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome","volume":"31","author":"Merino","year":"2007","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s40644-021-00392-9","article-title":"Imaging features of fumarate hydratase-deficient renal cell carcinomas: A retrospective study","volume":"21","author":"Nikolovski","year":"2021","journal-title":"Cancer Imaging"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1212\/WNL.40.3_Part_1.495","article-title":"Fumarase deficiency is an autosomal recessive encephalopathy affecting both the mitochondrial and the cytosolic enzymes","volume":"40","author":"Gellera","year":"1990","journal-title":"Neurology"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/ng849","article-title":"Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer","volume":"30","author":"Tomlinson","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/path.2932","article-title":"Aberrant succination of proteins in fumarate hydratase-deficient mice and HLRCC patients is a robust biomarker of mutation status","volume":"225","author":"Bardella","year":"2011","journal-title":"J. Pathol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1097\/PAS.0000000000000163","article-title":"Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cancer: Recognition of the syndrome by pathologic features and the utility of detecting aberrant succination by immunohistochemistry","volume":"38","author":"Chen","year":"2014","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1002\/cncr.33997","article-title":"Fumarate hydratase variant prevalence and manifestations among individuals receiving germline testing","volume":"128","author":"Lu","year":"2021","journal-title":"Cancer"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1007\/s10689-014-9735-2","article-title":"Hereditary leiomyomatosis and renal cell cancer (HLRCC): Renal cancer risk, surveillance and treatment","volume":"13","author":"Menko","year":"2014","journal-title":"Fam. Cancer"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/j.1399-0004.2010.01486.x","article-title":"Hereditary leiomyomatosis and renal cell cancer in families referred for fumarate hydratase germline mutation analysis","volume":"79","author":"Smit","year":"2011","journal-title":"Clin. Genet."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"738822","DOI":"10.3389\/fonc.2021.738822","article-title":"Birt-Hogg-Dube Syndrome and Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome: An Effective Multidisciplinary Approach to Hereditary Renal Cancer Predisposing Syndromes","volume":"11","author":"Marfan","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"3345","DOI":"10.1158\/1078-0432.CCR-13-0304","article-title":"Molecular pathways: Fumarate hydratase-deficient kidney cancer--targeting the Warburg effect in cancer","volume":"19","author":"Linehan","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.cancergencyto.2009.08.018","article-title":"UOK 262 cell line, fumarate hydratase deficient (FH-\/FH-) hereditary leiomyomatosis renal cell carcinoma: In vitro and in vivo model of an aberrant energy metabolic pathway in human cancer","volume":"196","author":"Yang","year":"2010","journal-title":"Cancer Genet. Cytogenet."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"9371","DOI":"10.1038\/s41598-021-88585-x","article-title":"Proteogenomic landscape of uterine leiomyomas from hereditary leiomyomatosis and renal cell cancer patients","volume":"11","author":"Bateman","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"eabc4436","DOI":"10.1126\/scisignal.abc4436","article-title":"Mitochondrial DNA alterations underlie an irreversible shift to aerobic glycolysis in fumarate hydratase-deficient renal cancer","volume":"14","author":"Crooks","year":"2021","journal-title":"Sci. Signal."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1158\/1078-0432.CCR-13-2993","article-title":"New strategies in renal cell carcinoma: Targeting the genetic and metabolic basis of disease","volume":"21","author":"Srinivasan","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Thompson, A.J., Alwan, Y.M., Ramani, V.A.C., Evans, D.G., Maher, E.R., and Woodward, E.R. (2022). Cost-effectiveness model of renal cell carcinoma (RCC) surveillance in hereditary leiomyomatosis and renal cell carcinoma (HLRCC). J. Med. Genet.","DOI":"10.1136\/jmedgenet-2021-108215"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1136\/jmg.2010.085068","article-title":"Novel FH mutations in families with hereditary leiomyomatosis and renal cell cancer (HLRCC) and patients with isolated type 2 papillary renal cell carcinoma","volume":"48","author":"Gardie","year":"2011","journal-title":"J. Med. Genet."},{"key":"ref_146","unstructured":"National Comprehensive Cancer Network (2022, August 02). Kidney Cancer 2019. Available online: https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/kidney.pdf."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/S0959-8049(14)70131-5","article-title":"5 Mechanism based targeted therapy for hereditary leimyomatosis and renal cell cancer (HLRCC) and sporadic papillary renal cell carcinoma\u201d interim results from a phase 2 study of bevacizumab and erlotinib","volume":"50","author":"Srinivasan","year":"2014","journal-title":"Eur. J. Cancer"},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Xu, Y., Kong, W., Cao, M., Wang, J., Wang, Z., Zheng, L., Wu, X., Cheng, R., He, W., and Yang, B. (2022). Genomic Profiling and Response to Immune Checkpoint Inhibition plus Tyrosine Kinase Inhibition in FH-Deficient Renal Cell Carcinoma. Eur. Urol.","DOI":"10.1016\/j.eururo.2022.05.029"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s10689-020-00195-0","article-title":"Complete response of hereditary leiomyomatosis and renal cell cancer (HLRCC)-associated renal cell carcinoma to nivolumab and ipilimumab combination immunotherapy by: A case report","volume":"20","author":"Iribe","year":"2021","journal-title":"Fam. Cancer"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"735077","DOI":"10.3389\/fonc.2021.735077","article-title":"Complete Response of Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC)-Associated Renal Cell Carcinoma to Pembrolizumab Immunotherapy: A Case Report","volume":"11","author":"Wang","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1038\/ng.912","article-title":"Germline BAP1 mutations predispose to malignant mesothelioma","volume":"43","author":"Testa","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1158\/1541-7786.MCR-13-0111","article-title":"A novel germline mutation in BAP1 predisposes to familial clear-cell renal cell carcinoma","volume":"11","author":"Farley","year":"2013","journal-title":"Mol. Cancer Res."},{"key":"ref_153","first-page":"4236","article-title":"Inherited predisposition to malignant mesothelioma: Germline BAP1 mutations and beyond","volume":"25","author":"Pagliuca","year":"2021","journal-title":"Eur. Rev. Med. Pharm. Sci."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/ng.2323","article-title":"BAP1 loss defines a new class of renal cell carcinoma","volume":"44","author":"Liao","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1002\/cncr.28521","article-title":"Loss of BAP1 protein expression is an independent marker of poor prognosis in patients with low-risk clear cell renal cell carcinoma","volume":"120","author":"Joseph","year":"2014","journal-title":"Cancer"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.juro.2015.07.113","article-title":"Clear cell renal cell carcinoma subtypes identified by BAP1 and PBRM1 expression","volume":"195","author":"Joseph","year":"2016","journal-title":"J. Urol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"e11","DOI":"10.1016\/j.urolonc.2016.03.006","article-title":"Loss of nuclear BAP1 protein expression is a marker of poor prognosis in patients with clear cell renal cell carcinoma","volume":"34","author":"Minardi","year":"2016","journal-title":"Urol. Oncol."},{"key":"ref_158","unstructured":"Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J.H., and Gripp, K.W. (1993). BAP1 Tumor Predisposition Syndrome. GeneReviews\u00ae, University of Washington."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/j.jtho.2022.03.014","article-title":"Medical and Surgical Care of Patients With Mesothelioma and Their Relatives Carrying Germline BAP1 Mutations","volume":"17","author":"Carbone","year":"2022","journal-title":"J. Thorac. Oncol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"154","DOI":"10.5858\/arpa.2020-0413-OA","article-title":"Improving Renal Tumor Biopsy Prognostication With BAP1 Analyses","volume":"146","author":"Kapur","year":"2022","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"28643","DOI":"10.1074\/jbc.M115.661553","article-title":"The BAP1\/ASXL2 Histone H2A Deubiquitinase Complex Regulates Cell Proliferation and Is Disrupted in Cancer","volume":"290","author":"Daou","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1093\/jnci\/djy171","article-title":"Comprehensive Study of the Clinical Phenotype of Germline BAP1 Variant-Carrying Families Worldwide","volume":"110","author":"Walpole","year":"2018","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1073\/pnas.1309085110","article-title":"Tumor suppressor and deubiquitinase BAP1 promotes DNA double-strand break repair","volume":"111","author":"Yu","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Lee, S.A., Lee, D., Kang, M., Kim, S., Kwon, S.J., Lee, H.S., Seo, H.R., Kaushal, P., Lee, N.S., and Kim, H. (2022). BAP1 promotes the repair of UV-induced DNA damage via PARP1-mediated recruitment to damage sites and control of activity and stability. Cell Death Differ.","DOI":"10.1038\/s41418-022-01024-w"},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Baas, R., van der Wal, F.J., Bleijerveld, O.B., van Attikum, H., and Sixma, T.K. (2021). Proteomic analysis identifies novel binding partners of BAP1. PLoS ONE, 16.","DOI":"10.1101\/2021.03.03.433804"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/s41418-020-00709-4","article-title":"Roles and mechanisms of BAP1 deubiquitinase in tumor suppression","volume":"28","author":"Masclef","year":"2021","journal-title":"Cell Death Differ."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1038\/nature22798","article-title":"BAP1 regulates IP3R3-mediated Ca 2+ flux to mitochondria suppressing cell transformation","volume":"546","author":"Bononi","year":"2017","journal-title":"Nature"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.ejca.2017.12.022","article-title":"Germline BAP1-positive patients: The dilemmas of cancer surveillance and a proposed interdisciplinary consensus monitoring strategy","volume":"92","author":"Star","year":"2018","journal-title":"Eur. J. Cancer"},{"key":"ref_169","first-page":"81","article-title":"Sclerose tubereuse der circonvolutions cerebrales: Idiotie et epilepsie hemiplegique","volume":"1","author":"Bourneville","year":"1880","journal-title":"Arch. Neurol."},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Kwiatkowski, D.J., Whittemore, V.H., and Thiele, E.A. (2011). Tuberous Sclerosis Complex: Genes, Clinical Features and Therapeutics, John Wiley & Sons.","DOI":"10.1002\/9783527630073"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/ng0992-37","article-title":"Linkage of an important gene locus for tuberous sclerosis to a chromosome 16 marker for polycystic kidney disease","volume":"2","author":"Kandt","year":"1992","journal-title":"Nat. Genet."},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"European Chromosome 16 Tuberous Sclerosis Consortium (1993). Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell, 75, 1305\u20131315.","DOI":"10.1016\/0092-8674(93)90618-Z"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1126\/science.277.5327.805","article-title":"Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34","volume":"277","author":"Hermans","year":"1997","journal-title":"Science"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0387-7604(80)80031-3","article-title":"Tuberous sclerosis: The incidence of familial versus sporadic cases","volume":"2","author":"Fleury","year":"1980","journal-title":"Brain Dev."},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"Henske, E.P., Cornejo, K.M., and Wu, C.L. (2021). Renal Cell Carcinoma in Tuberous Sclerosis Complex. Genes, 12.","DOI":"10.3390\/genes12101585"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.acra.2020.12.019","article-title":"Tuberous Sclerosis Complex (TSC): Renal and Extrarenal Imaging","volume":"29","author":"Gupta","year":"2021","journal-title":",Acad. Radiol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1007\/s00467-018-4003-6","article-title":"Renal progression factors in young patients with tuberous sclerosis complex: A retrospective cohort study","volume":"33","author":"Janssens","year":"2018","journal-title":"Pediatr. Nephrol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1038\/sj.ki.5001853","article-title":"Renal manifestations of tuberous sclerosis complex: Incidence, prognosis, and predictive factors","volume":"70","author":"Rakowski","year":"2006","journal-title":"Kidney Int."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1016\/j.juro.2015.07.126","article-title":"Update on the diagnosis and management of renal angiomyolipoma","volume":"195 Pt. 1","author":"Flum","year":"2016","journal-title":"J. Urol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/j.urology.2008.07.049","article-title":"Changing trends in presentation, diagnosis and management of renal angiomyolipoma: Comparison of sporadic and tuberous sclerosis complex-associated forms","volume":"72","author":"Seyam","year":"2008","journal-title":"Urology"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1097\/PAS.0000000000000248","article-title":"Tuberous sclerosis\u2013associated renal cell carcinoma: A clinicopathologic study of 57 separate carcinomas in 18 patients","volume":"38","author":"Guo","year":"2014","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1097\/PAS.0000000000000237","article-title":"Renal cell carcinoma in tuberous sclerosis complex","volume":"38","author":"Yang","year":"2014","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1016\/j.mayocp.2020.11.004","article-title":"Renal Neoplasia in Tuberous Sclerosis: A Study of 41 Patients","volume":"96","author":"Gupta","year":"2021","journal-title":"Mayo Clin. Proc."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1042\/BJ20080281","article-title":"The TSC1-TSC2 complex: A molecular switchboard controlling cell growth","volume":"412","author":"Huang","year":"2008","journal-title":"Biochem. J."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.cell.2006.01.016","article-title":"TOR signaling in growth and metabolism","volume":"124","author":"Wullschleger","year":"2006","journal-title":"Cell"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jdermsci.2015.04.005","article-title":"Mammalian target of rapamycin and tuberous sclerosis complex","volume":"79","year":"2015","journal-title":"J. Derm. Sci."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1016\/j.urology.2007.07.045","article-title":"The Role of Partial Nephrectomy for the Management of Sporadic Renal Angiomyolipoma","volume":"70","author":"Boorjian","year":"2007","journal-title":"Urology"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S0302-2838(02)00015-5","article-title":"Nephron-sparing surgery for renal angiomyolipoma","volume":"41","author":"Heidenreich","year":"2002","journal-title":"Eur. Urol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1016\/S0022-5347(17)35895-0","article-title":"The natural history of renal angiomyolipoma","volume":"150","author":"Steiner","year":"1993","journal-title":"J. Urol."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0022-5347(17)32809-4","article-title":"The evolution of renal angiomyolipomas in patients with tuberous sclerosis","volume":"152","author":"Smits","year":"1994","journal-title":"J. Urol."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1111\/bju.12604","article-title":"Active surveillance for renal angiomyolipoma: Outcomes and factors predictive of delayed intervention","volume":"114","author":"Ouzaid","year":"2014","journal-title":"BJU Int."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1148\/radiol.2251011477","article-title":"Renal angiomyolipoma: Relationships between tumor size, aneurysm formation, and rupture","volume":"225","author":"Yamakado","year":"2002","journal-title":"Radiology"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/S0140-6736(12)61767-X","article-title":"Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): A multicentre, randomised, double-blind, placebo-controlled trial","volume":"381","author":"Bissler","year":"2013","journal-title":"Lancet"},{"key":"ref_194","doi-asserted-by":"crossref","unstructured":"Bissler, J.J., Nonomura, N., Budde, K., Zonnenberg, B.A., Fischereder, M., Voi, M., Louveau, A.L., Herbst, F., Bebin, E.M., and Curatolo, P. (2018). Angiomyolipoma rebound tumor growth after discontinuation of everolimus in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0201005"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1002\/pbc.22401","article-title":"Sirolimus therapy for fibromatosis and multifocal renal cell carcinoma in a child with tuberous sclerosis complex","volume":"54","author":"Pressey","year":"2010","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/1752-1947-8-95","article-title":"The use of everolimus to target carcinogenic pathways in a patient with renal cell carcinoma and tuberous sclerosis complex: A case report","volume":"8","author":"Kim","year":"2014","journal-title":"J. Med. Case Rep."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"a002220","DOI":"10.1101\/mcs.a002220","article-title":"Exceptional response to everolimus in a novel tuberous sclerosis complex-2 mutation-associated metastatic renal-cell carcinoma","volume":"4","author":"Alsidawi","year":"2018","journal-title":"Cold Spring Harb. Mol. Case Stud."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.pediatrneurol.2013.08.002","article-title":"Tuberous sclerosis complex surveillance and management: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference","volume":"49","author":"Krueger","year":"2013","journal-title":"Pediatr. Neurol."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1001\/archderm.1977.01640120042005","article-title":"Hereditary multiple fibrofolliculomas with trichodiscomas and acrochordons","volume":"113","author":"Birt","year":"1977","journal-title":"Arch. Dermatol."},{"key":"ref_200","first-page":"928","article-title":"Fibromes p\u00e9rifolliculaires polypose colique familiale pneumothorax spontan\u00e9s familiaux","volume":"113","author":"Binet","year":"1986","journal-title":"Ann. Dermatol. V\u00e9n\u00e9r\u00e9ol."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/S0190-9622(08)82049-X","article-title":"Bilateral renal cell carcinoma in the Birt-Hogg-Dub\u00e9 syndrome","volume":"29","author":"Roth","year":"1993","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1001\/archderm.135.10.1195","article-title":"Birt-Hogg-Dub\u00e9 syndrome: A novel marker of kidney neoplasia","volume":"135","author":"Toro","year":"1999","journal-title":"Arch. Dermatol."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.gene.2017.09.044","article-title":"FLCN: The causative gene for Birt-Hogg-Dub\u00e9 syndrome","volume":"640","author":"Schmidt","year":"2018","journal-title":"Gene"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S1535-6108(02)00104-6","article-title":"Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dub\u00e9 syndrome","volume":"2","author":"Nickerson","year":"2002","journal-title":"Cancer Cell"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/sj.jid.5700959","article-title":"Birt-Hogg-Dub\u00e9 syndrome: Clinical and genetic studies of 20 families","volume":"128","author":"Leter","year":"2008","journal-title":"J. Investig. Dermatol."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1038\/bjc.2011.463","article-title":"Renal cancer and pneumothorax risk in Birt-Hogg-Dub\u00e9 syndrome; an analysis of 115 FLCN mutation carriers from 35 BHD families","volume":"105","author":"Houweling","year":"2011","journal-title":"Br. J. Cancer"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1136\/jmg.2007.054304","article-title":"BHD mutations, clinical and molecular genetic investigations of Birt-Hogg-Dub\u00e9 syndrome: A new series of 50 families and a review of published reports","volume":"45","author":"Toro","year":"2008","journal-title":"J. Med. Genet."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1097\/00000478-200212000-00002","article-title":"Renal tumors in the Birt-Hogg-Dub\u00e9 syndrome","volume":"26","author":"Pavlovich","year":"2002","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1093\/jnci\/djm288","article-title":"Kidney-targeted Birt-Hogg-Dube gene inactivation in a mouse model: Erk1\/2 and Akt-mTOR activation, cell hyperproliferation, and polycystic kidneys","volume":"100","author":"Baba","year":"2008","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1038\/ki.2015.177","article-title":"Disruption of tubular Flcn expression as a mouse model for renal tumor induction","volume":"88","author":"Chen","year":"2015","journal-title":"Kidney Int."},{"key":"ref_211","doi-asserted-by":"crossref","unstructured":"Gijezen, L.M., Vernooij, M., Martens, H., Oduber, C.E., Henquet, C.J., Starink, T.M., Prins, M.H., Menko, F.H., Nelemans, P.J., and van Steensel, M.A. (2014). Topical rapamycin as a treatment for fibrofolliculomas in Birt-Hogg-Dub\u00e9 syndrome: A double-blind placebo-controlled randomized split-face trial. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0099071"},{"key":"ref_212","doi-asserted-by":"crossref","unstructured":"Hong, S.B., Oh, H., Valera, V.A., Baba, M., Schmidt, L.S., and Linehan, W.M. (2010). Inactivation of the FLCN tumor suppressor gene induces TFE3 transcriptional activity by increasing its nuclear localization. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0015793"},{"key":"ref_213","first-page":"ra42","article-title":"The transcription factor TFEB links mTORC1 signaling to transcriptional control of lysosome homeostasis","volume":"5","author":"Petit","year":"2012","journal-title":"Sci. Signal."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1083\/jcb.201307084","article-title":"Recruitment of folliculin to lysosomes supports the amino acid-dependent activation of Rag GTPases","volume":"202","author":"Petit","year":"2013","journal-title":"J. Cell Biol."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/s41586-020-2444-0","article-title":"A substrate-specific mTORC1 pathway underlies Birt-Hogg-Dube syndrome","volume":"585","author":"Napolitano","year":"2020","journal-title":"Nature"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"15866","DOI":"10.1038\/ncomms15866","article-title":"Negative regulation of EGFR signalling by the human folliculin tumour suppressor protein","volume":"8","author":"Laviolette","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"4383","DOI":"10.1093\/hmg\/ddt288","article-title":"Birt-Hogg-Dube syndrome is a novel ciliopathy","volume":"22","author":"Luijten","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.celrep.2014.03.025","article-title":"Folliculin controls lung alveolar enlargement and epithelial cell survival through E-cadherin, LKB1, and AMPK","volume":"7","author":"Goncharov","year":"2014","journal-title":"Cell Rep."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1038\/onc.2010.497","article-title":"Absence of the Birt-Hogg-Dub\u00e9 gene product is associated with increased hypoxia-inducible factor transcriptional activity and a loss of metabolic flexibility","volume":"30","author":"Preston","year":"2011","journal-title":"Oncogene"},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/S1470-2045(09)70188-3","article-title":"Birt-Hogg-Dub\u00e9 syndrome: Diagnosis and management","volume":"10","author":"Menko","year":"2009","journal-title":"Lancet Oncol."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.6004\/jnccn.2020.0043","article-title":"NCCN Guidelines Insights: Kidney Cancer, Version 1.2021: Featured Updates to the NCCN Guidelines","volume":"18","author":"Motzer","year":"2020","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s10689-013-9657-4","article-title":"Diagnosis and management of BHD-associated kidney cancer","volume":"12","author":"Stamatakis","year":"2013","journal-title":"Fam. Cancer"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.2214\/AJR.17.18071","article-title":"The ABCs of BHD: An In-Depth Review of Birt-Hogg-Dub\u00e9 Syndrome","volume":"209","author":"Gupta","year":"2017","journal-title":"AJR Am. J. Roentgenol."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1148\/radiol.2021211972","article-title":"Birt-Hogg-Dub\u00e9 Syndrome","volume":"302","author":"Ghosh","year":"2022","journal-title":"Radiology"},{"key":"ref_225","first-page":"1257","article-title":"Renal hybrid oncocytic\/chromophobe tumors\u2014A review","volume":"28","author":"Hes","year":"2013","journal-title":"Histol Histopathol."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1097\/01.ju.0000154629.45832.30","article-title":"Evaluation and management of renal tumors in the Birt-Hogg-Dube syndrome","volume":"173","author":"Pavlovich","year":"2005","journal-title":"J. Urol."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"3898","DOI":"10.1158\/1078-0432.CCR-18-0252","article-title":"Identification and Validation of Radiographic Enhancement for Reliable Differentiation of CD117(+) Benign Renal Oncocytoma and Chromophobe Renal Cell Carcinoma","volume":"24","author":"Amin","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1093\/hmg\/5.9.1333","article-title":"The t(X.;1)(p11.2;q21.2) translocation in papillary renal cell carcinoma fuses a novel gene PRCC to the TFE3 transcription factor gene","volume":"5","author":"Sidhar","year":"1996","journal-title":"Hum. Mol. Genet."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/nature10539","article-title":"A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma","volume":"480","author":"Bertolotto","year":"2011","journal-title":"Nature"},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.urology.2020.11.025","article-title":"Clinical and Molecular Characterization of Microphthalmia-associated Transcription Factor (MITF)-related Renal Cell Carcinoma","volume":"149","author":"Lang","year":"2021","journal-title":"Urology"},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1053\/j.semdp.2015.02.003","article-title":"MiT family translocation renal cell carcinoma","volume":"32","author":"Argani","year":"2015","journal-title":"Semin. Diagn. Pathol."},{"key":"ref_232","first-page":"125","article-title":"MiT family translocation renal cell carcinomas: A 15th anniversary update","volume":"35","author":"Gandhi","year":"2020","journal-title":"Histol. Histopathol."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"ra9","DOI":"10.1126\/scisignal.2004754","article-title":"The nutrient-responsive transcription factor TFE3 promotes autophagy, lysosomal biogenesis, and clearance of cellular debris","volume":"7","author":"Martina","year":"2014","journal-title":"Sci. Signal."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1111\/pcmr.12370","article-title":"Microphthalmia-associated transcription factor in melanoma development and MAP-kinase pathway targeted therapy","volume":"28","author":"Wellbrock","year":"2015","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/nrurol.2014.162","article-title":"Molecular genetics and cellular features of TFE3 and TFEB fusion kidney cancers","volume":"11","author":"Kauffman","year":"2014","journal-title":"Nat. Rev. Urol."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/j.1755-148X.2008.00518.x","article-title":"Gpnmb is a melanoblast-expressed, MITF-dependent gene","volume":"22","author":"Loftus","year":"2009","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"3619","DOI":"10.1200\/JCO.2013.52.5683","article-title":"Phase I\/II study of the antibody-drug conjugate glembatumumab vedotin in patients with locally advanced or metastatic breast cancer","volume":"32","author":"Bendell","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"3659","DOI":"10.1200\/JCO.2013.54.8115","article-title":"Phase I\/II study of the antibody-drug conjugate glembatumumab vedotin in patients with advanced melanoma","volume":"32","author":"Ott","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1200\/JCO.2014.56.2959","article-title":"EMERGE: A Randomized Phase II Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Advanced Glycoprotein NMB-Expressing Breast Cancer","volume":"33","author":"Yardley","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1245\/s10434-020-08813-y","article-title":"Nephron-Sparing Surgery for Adult Xp11.2 Translocation Renal Cell Carcinoma at Clinical T1 Stage: A Multicenter Study in China","volume":"28","author":"Liu","year":"2021","journal-title":"Ann. Surg. Oncol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/11\/2122\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:18:48Z","timestamp":1760145528000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/11\/2122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,15]]},"references-count":240,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["genes13112122"],"URL":"https:\/\/doi.org\/10.3390\/genes13112122","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,15]]}}}