{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T15:16:44Z","timestamp":1790954204397,"version":"4.1.0"},"reference-count":27,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100007270","name":"University of Michigan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007270","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Human Pathology"],"published-print":{"date-parts":[[2022,12]]},"DOI":"10.1016\/j.humpath.2022.10.009","type":"journal-article","created":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T18:55:27Z","timestamp":1666896927000},"page":"95-109","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":8,"special_numbering":"C","title":["Deciphering intratumor heterogeneity in clear cell renal cell carcinoma utilizing clinicopathologic and molecular platforms"],"prefix":"10.1016","volume":"130","author":[{"given":"Erica","family":"Vormittag-Nocito","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Mannan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anya","family":"Chinnaiyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Zelenka-Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuhong","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd M.","family":"Morgan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled","family":"Hafez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulka","family":"Vaishampayan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman","family":"Abdulfatah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arul M.","family":"Chinnaiyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saravana M.","family":"Dhanasekaran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohit","family":"Mehra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.humpath.2022.10.009_bib1","author":"Surveillance","year":"2019"},{"key":"10.1016\/j.humpath.2022.10.009_bib2","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1093\/ajcp\/aqaa176","article-title":"BAP1-Mutated Clear Cell Renal Cell Carcinoma: A Clinicopathologic Characterization of 14 Molecularly Confirmed Tumors","volume":"155","author":"Gallan","year":"2021","journal-title":"Am J Clin Pathol"},{"key":"10.1016\/j.humpath.2022.10.009_bib3","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.neo.2018.12.006","article-title":"Expression and Mutation Patterns of PBRM1, BAP1 and SETD2 Mirror Specific Evolutionary Subtypes in Clear Cell Renal Cell Carcinoma","volume":"21","author":"Bihr","year":"2019","journal-title":"Neoplasia"},{"key":"10.1016\/j.humpath.2022.10.009_bib4","doi-asserted-by":"crossref","first-page":"243.e1","DOI":"10.1016\/j.urolonc.2018.01.002","article-title":"Prognostic impact of concomitant loss of PBRM1 and BAP1 protein expression in early stages of clear cell renal cell carcinoma","volume":"36","author":"Da Costa","year":"2018","journal-title":"Urol Oncol"},{"key":"10.1016\/j.humpath.2022.10.009_bib5","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/nature12222","article-title":"Comprehensive molecular characterization of clear cell renal cell carcinoma","volume":"499","author":"Cancer Genome Atlas Research Network","year":"2013","journal-title":"Nature"},{"key":"10.1016\/j.humpath.2022.10.009_bib6","doi-asserted-by":"crossref","DOI":"10.1186\/s12894-017-0209-3","article-title":"BAP1 and PBRM1 in metastatic clear cell renal cell carcinoma: tumor heterogeneity and concordance with paired primary tumor","volume":"17","author":"Eckel-Passow","year":"2017","journal-title":"BMC Urol"},{"key":"10.1016\/j.humpath.2022.10.009_bib7","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.urolonc.2017.02.003","article-title":"Loss of BAP1 protein expression in the first metastatic site predicts prognosis in patients with clear cell renal cell carcinoma","volume":"35","author":"Miura","year":"2017","journal-title":"Urol Oncol"},{"key":"10.1016\/j.humpath.2022.10.009_bib8","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1056\/NEJMoa1113205","article-title":"Intratumor heterogeneity and branched evolution revealed by multiregion sequencing","volume":"366","author":"Gerlinger","year":"2012","journal-title":"N Engl J Med"},{"key":"10.1016\/j.humpath.2022.10.009_bib9","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1038\/modpathol.2015.68","article-title":"Intratumoral morphologic and molecular heterogeneity of rhabdoid renal cell carcinoma: challenges for personalized therapy","volume":"28","author":"Singh","year":"2015","journal-title":"Mod Pathol"},{"key":"10.1016\/j.humpath.2022.10.009_bib10","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":"10.1016\/j.humpath.2022.10.009_bib11","doi-asserted-by":"crossref","unstructured":"Mannan R, Li Y, Chen S et al. Integrated Clinico-Pathological and Proteogenomic Characterization of Clear Cell Renal Cell Carcinoma by the Clinical Proteomic Tumor Analysis Consortium (CPTAC). Lab Invest (Suppl 1):522-659. https:\/\/doi.org\/10.1038\/s41374-022-00755-1","DOI":"10.1038\/s41374-022-00755-1"},{"key":"10.1016\/j.humpath.2022.10.009_bib12","article-title":"Histopathologic and proteogenomic heterogeneity reveals features of clear cell renal cell carcinoma aggressiveness","author":"Li","year":"2022","journal-title":"Cancer Cell"},{"key":"10.1016\/j.humpath.2022.10.009_bib13","doi-asserted-by":"crossref","DOI":"10.1186\/1479-5876-7-90","article-title":"Epigenetic control of the ubiquitin carboxyl terminal hydrolase 1 in renal cell carcinoma","volume":"7","author":"Seliger","year":"2009","journal-title":"J Transl Med"},{"key":"10.1016\/j.humpath.2022.10.009_bib14","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1158\/1078-0432.CCR-06-0824","article-title":"Ubiquitin COOH-terminal hydrolase 1: a biomarker of renal cell carcinoma associated with enhanced tumor cell proliferation and migration","volume":"13","author":"Seliger","year":"2007","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.humpath.2022.10.009_bib15","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2020.592501","article-title":"Ubiquitin Carboxyl-Terminal Hydrolases and Human Malignancies: The Novel Prognostic and Therapeutic Implications for Head and Neck Cancer","volume":"10","author":"Rong","year":"2021","journal-title":"Front Oncol"},{"key":"10.1016\/j.humpath.2022.10.009_bib16","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41416-021-01516-5","article-title":"UCHL1 as a novel target in breast cancer: emerging insights from cell and chemical biology","volume":"126","author":"Mondal","year":"2021","journal-title":"Br J Cancer"},{"key":"10.1016\/j.humpath.2022.10.009_bib17","doi-asserted-by":"crossref","unstructured":"Vormittag-Nocitio E, Mannan R, Wang X et al. Deciphering Intratumor Heterogeneity in Clear Cell Renal Cell Carcinoma Utilizing Clinicopathologic and Molecular Platforms. Lab Invest (Suppl 1):522-659. doi: 10.1038\/s41374-022-00755-1","DOI":"10.1038\/s41374-022-00755-1"},{"key":"10.1016\/j.humpath.2022.10.009_bib18","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/nrm3274","article-title":"Understanding the language of Lys36 methylation at histone H3","volume":"13","author":"Wagner","year":"2012","journal-title":"Nat Rev Mol Cell Biol"},{"key":"10.1016\/j.humpath.2022.10.009_bib19","doi-asserted-by":"crossref","first-page":"3259","DOI":"10.1158\/1078-0432.CCR-12-3886","article-title":"Adverse outcomes in clear cell renal cell carcinoma with mutations of 3p21 epigenetic regulators BAP1 and SETD2: a report by MSKCC and the KIRC TCGA research network","volume":"19","author":"Hakimi","year":"2013","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.humpath.2022.10.009_bib20","doi-asserted-by":"crossref","DOI":"10.1097\/MD.0000000000002004","article-title":"Decreased Expression of SETD2 Predicts Unfavorable Prognosis in Patients With Nonmetastatic Clear-Cell Renal Cell Carcinoma","volume":"94","author":"Liu","year":"2015","journal-title":"Medicine"},{"key":"10.1016\/j.humpath.2022.10.009_bib21","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.18632\/oncotarget.6481","article-title":"Dynamic reprogramming of DNA methylation in SETD2-deregulated renal cell carcinoma","volume":"12","author":"Tiedmann","year":"2016","journal-title":"Oncotarget"},{"key":"10.1016\/j.humpath.2022.10.009_bib22","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.neo.2016.04.005","article-title":"Functional Studies on Primary Tubular Epithelial Cells Indicate a Tumor Suppressor Role of SETD2 in Clear Cell Renal Cell Carcinoma","volume":"18","author":"Li","year":"2016","journal-title":"Neoplasia"},{"key":"10.1016\/j.humpath.2022.10.009_bib23","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2019.10.052","article-title":"Ontological analyses reveal clinically significant clear cell renal cell carcinoma subtypes with convergent evolutionary trajectories into an aggressive type","volume":"51","author":"Cai","year":"2020","journal-title":"EBioMedicine"},{"key":"10.1016\/j.humpath.2022.10.009_bib24","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/S1470-2045(12)70584-3","article-title":"Effects on survival of BAP1 and PBRM1 mutations in sporadic clear-cell renal-cell carcinoma: a retrospective analysis with independent validation","volume":"14","author":"Kapur","year":"2013","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.humpath.2022.10.009_bib25","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.trecan.2019.09.006","article-title":"BAP1 Missense Mutations in Cancer: Friend or Foe","volume":"5","author":"Okonska","year":"2019","journal-title":"Trends Cancer"},{"key":"10.1016\/j.humpath.2022.10.009_bib26","doi-asserted-by":"crossref","first-page":"338.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":"10.1016\/j.humpath.2022.10.009_bib27","doi-asserted-by":"crossref","DOI":"10.3390\/cancers13092163","article-title":"Spatial Distribution of Private Gene Mutations in Clear Cell Renal Cell Carcinoma","volume":"13","author":"Moore","year":"2021","journal-title":"Cancers (Basel)"}],"container-title":["Human Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0046817722002568?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0046817722002568?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T16:40:54Z","timestamp":1758645654000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0046817722002568"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12]]},"references-count":27,"alternative-id":["S0046817722002568"],"URL":"https:\/\/doi.org\/10.1016\/j.humpath.2022.10.009","relation":{},"ISSN":["0046-8177"],"issn-type":[{"value":"0046-8177","type":"print"}],"subject":[],"published":{"date-parts":[[2022,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Deciphering intratumor heterogeneity in clear cell renal cell carcinoma utilizing clinicopathologic and molecular platforms","name":"articletitle","label":"Article Title"},{"value":"Human Pathology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.humpath.2022.10.009","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}