{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T01:04:43Z","timestamp":1776387883134,"version":"3.51.2"},"reference-count":55,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T00:00:00Z","timestamp":1601424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Since the approval of PARP inhibitors for the treatment of high-grade serous ovarian cancer, in addition to cancer risk assessment, BRCA1 and BRCA2 genetic testing also has therapeutic implications (germline and somatic variants) and should be offered to these patients at diagnosis, irrespective of family history. However, variants in other genes besides BRCA1 and BRCA2 are associated with ovarian cancer predisposition, which would be missed by a genetic testing aimed only at indication for PARP inhibitor treatment. In this study, we aimed to evaluate the yield of clinically actionable germline variants using next-generation sequencing of a customized panel of 10 genes for the analysis of formalin-fixed paraffin-embedded samples from 96 ovarian carcinomas, a strategy that allows the detection of both somatic and germline variants in a single test. In addition to 13.7% of deleterious germline BRCA1\/BRCA2 carriers, we identified 7.4% additional patients with pathogenic germline variants in other genes predisposing for ovarian cancer, namely RAD51C, RAD51D, and MSH6, representing 35% of all pathogenic germline variants. We conclude that the strategy of reflex gene-panel tumor testing enables the identification of clinically actionable germline variants in a significantly higher proportion of ovarian cancer patients, which may be valuable information in patients with advanced disease that have run out of approved therapeutic options. Furthermore, this approach increases the chance to make available genetic counseling, presymptomatic genetic testing, and gynecological cancer prophylaxis to female relatives who turn out to be healthy carriers of deleterious germline variants.<\/jats:p>","DOI":"10.3390\/cancers12102834","type":"journal-article","created":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T09:04:12Z","timestamp":1601543052000},"page":"2834","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Gene Panel Tumor Testing in Ovarian Cancer Patients Significantly Increases the Yield of Clinically Actionable Germline Variants beyond BRCA1\/BRCA2"],"prefix":"10.3390","volume":"12","author":[{"given":"Ana","family":"Barbosa","sequence":"first","affiliation":[{"name":"Cancer Genetics Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6289-5792","authenticated-orcid":false,"given":"Pedro","family":"Pinto","sequence":"additional","affiliation":[{"name":"Cancer Genetics Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"}]},{"given":"Ana","family":"Peixoto","sequence":"additional","affiliation":[{"name":"Cancer Genetics Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"},{"name":"Department of Genetics, Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"}]},{"given":"Joana","family":"Guerra","sequence":"additional","affiliation":[{"name":"Cancer Genetics Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8689-3388","authenticated-orcid":false,"given":"Carla","family":"Pinto","sequence":"additional","affiliation":[{"name":"Cancer Genetics Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"},{"name":"Department of Genetics, Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"}]},{"given":"Catarina","family":"Santos","sequence":"additional","affiliation":[{"name":"Cancer Genetics Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"},{"name":"Department of Genetics, Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"}]},{"given":"Manuela","family":"Pinheiro","sequence":"additional","affiliation":[{"name":"Cancer Genetics Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8809-4894","authenticated-orcid":false,"given":"Carla","family":"Escudeiro","sequence":"additional","affiliation":[{"name":"Cancer Genetics Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"}]},{"given":"Carla","family":"Bartosch","sequence":"additional","affiliation":[{"name":"Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"}]},{"given":"Jo\u00e3o","family":"Silva","sequence":"additional","affiliation":[{"name":"Cancer Genetics Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"},{"name":"Department of Genetics, Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4896-5982","authenticated-orcid":false,"given":"Manuel R.","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Cancer Genetics Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"},{"name":"Department of Genetics, Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA A Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.clon.2005.05.009","article-title":"Epithelial Ovarian Cancer: A Review of Current Management","volume":"17","author":"Guppy","year":"2005","journal-title":"Clin. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1007\/s12094-016-1588-8","article-title":"SEOM Clinical Guideline in ovarian cancer","volume":"18","author":"Santaballa","year":"2016","journal-title":"Clin. Transl. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.6004\/jnccn.2016.0122","article-title":"Ovarian Cancer, Version 1.2016, NCCN Clinical Practice Guidelines in Oncology","volume":"14","author":"Morgan","year":"2016","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"viii51","DOI":"10.1093\/annonc\/mdx441","article-title":"Treatment of recurrent ovarian cancer","volume":"28","author":"Pignata","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"iv259","DOI":"10.1093\/annonc\/mdy157","article-title":"ESMO Guidelines Working Group Corrections to \u201cNewly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up\u201d","volume":"29","author":"Ledermann","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/S1470-2045(14)70228-1","article-title":"Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: A preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial","volume":"15","author":"Ledermann","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1056\/NEJMoa1105535","article-title":"Olaparib Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian Cancer","volume":"366","author":"Ledermann","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.1056\/NEJMoa1810858","article-title":"Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer","volume":"379","author":"Moore","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3785","DOI":"10.1200\/JCO.2008.16.0812","article-title":"A Synthetic Lethal Therapeutic Approach: Poly(ADP) Ribose Polymerase Inhibitors for the Treatment of Cancers Deficient in DNA Double-Strand Break Repair","volume":"26","author":"Ashworth","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1053\/j.seminoncol.2017.08.004","article-title":"Guidance Statement on BRCA1\/2 Tumor Testing in Ovarian Cancer Patients","volume":"44","author":"Capoluongo","year":"2017","journal-title":"Semin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"18032","DOI":"10.1073\/pnas.1115052108","article-title":"Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing","volume":"108","author":"Walsh","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.1001\/jama.2017.7112","article-title":"Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers","volume":"317","author":"Kuchenbaecker","year":"2017","journal-title":"JAMA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1001\/jamaoncol.2015.5495","article-title":"Inherited Mutations in Women With Ovarian Carcinoma","volume":"2","author":"Norquist","year":"2016","journal-title":"JAMA Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.jmoldx.2016.10.002","article-title":"Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists","volume":"19","author":"Li","year":"2017","journal-title":"J. Mol. Diagn."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.3389\/fonc.2020.01318","article-title":"Tumor Testing for Somatic and Germline BRCA1\/BRCA2 Variants in Ovarian Cancer Patients in the Context of Strong Founder Effects","volume":"10","author":"Peixoto","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.ajhg.2017.12.013","article-title":"Assessment of the Clinical Relevance of BRCA2 Missense Variants by Functional and Computational Approaches","volume":"102","author":"Guidugli","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1002\/humu.23818","article-title":"Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification","volume":"40","author":"Parsons","year":"2019","journal-title":"Hum. Mutat."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1136\/jmedgenet-2018-105792","article-title":"Prevalence of germline pathogenic BRCA1\/2 variants in sequential epithelial ovarian cancer cases","volume":"56","author":"Morgan","year":"2019","journal-title":"J. Med. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"The Cancer Genome Atlas Research Network (2011). Integrated genomic analyses of ovarian carcinoma. Nature, 474, 609\u2013615.","DOI":"10.1038\/nature10166"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.ygyno.2011.01.020","article-title":"Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer","volume":"121","author":"Zhang","year":"2011","journal-title":"Gynecol. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1158\/1078-0432.CCR-13-2287","article-title":"Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas","volume":"20","author":"Pennington","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4026","DOI":"10.1038\/srep04026","article-title":"Clinical Characteristics of Ovarian Cancer Classified by BRCA1, BRCA2 and RAD51C Status","volume":"4","author":"Cunningham","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1038\/nsmb.1927","article-title":"Rad51 protects nascent DNA from Mre11-dependent degradation and promotes continuous DNA synthesis","volume":"17","author":"Hashimoto","year":"2010","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1038\/ng.569","article-title":"Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene","volume":"42","author":"Meindl","year":"2010","journal-title":"Nat. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1038\/ng.893","article-title":"Germline mutations in RAD51D confer susceptibility to ovarian cancer","volume":"43","author":"Loveday","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2901","DOI":"10.1200\/JCO.2015.61.2408","article-title":"Contribution of Germline Mutations in the RAD51B, RAD51C, and RAD51D Genes to Ovarian Cancer in the Population","volume":"33","author":"Song","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Harter, P., Hauke, J., Heitz, F., Reuss, A., Kommoss, S., Marme, F., Heimbach, A., Prieske, K., Richtees, L., and Burges, A. (2017). Prevalence of deleterious germline variants in risk genes including BRCA1\/2 in consecutive ovarian cancer patients (AGO-TR-1). PLoS ONE, 12.","DOI":"10.1200\/JCO.2016.34.15_suppl.5538"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1038\/s10038-018-0498-8","article-title":"Contribution of RAD51D germline mutations in breast and ovarian cancer in Greece","volume":"63","author":"Konstanta","year":"2018","journal-title":"J. Hum. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/ng.2224","article-title":"Germline RAD51C mutations confer susceptibility to ovarian cancer","volume":"44","author":"Loveday","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Yang, X., Song, H., Leslie, G., Engel, C., Hahnen, E., Auber, B., Horv\u00e1th, J., Kast, K., Niederacher, D., and Turnbull, C. (2020). Ovarian and Breast Cancer Risks Associated With Pathogenic Variants in RAD51C and RAD51D. J. Natl. Cancer Inst.","DOI":"10.1093\/jnci\/djaa030"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"9","DOI":"10.6004\/jnccn.2017.0003","article-title":"NCCN Guidelines Insights: Genetic\/Familial High-Risk Assessment: Breast and Ovarian, Version 2.2017","volume":"15","author":"Daly","year":"2016","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/nrc3878","article-title":"Milestones of Lynch syndrome: 1895\u20132015","volume":"15","author":"Lynch","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1002\/ijc.23508","article-title":"The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome","volume":"123","author":"Watson","year":"2008","journal-title":"Int. J. Cancer"},{"key":"ref_35","first-page":"1306","article-title":"Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years of age: A report from the Prospective Lynch Syndrome Database","volume":"67","author":"Bernstein","year":"2017","journal-title":"Gut"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1897-4287-7-17","article-title":"Cancer risk in MLH1, MSH2 and MSH6 mutation carriers; different risk profiles may influence clinical management","volume":"7","author":"Ramsoekh","year":"2009","journal-title":"Hered. Cancer Clin. Pract."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2304","DOI":"10.1001\/jama.2011.743","article-title":"Cancer Risks Associated With Germline Mutations in MLH1, MSH2, and MSH6 Genes in Lynch Syndrome","volume":"305","author":"Bonadona","year":"2011","journal-title":"JAMA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1038\/ng1627","article-title":"The BRIP1 helicase functions independently of BRCA1 in the Fanconi anemia pathway for DNA crosslink repair","volume":"37","author":"Bridge","year":"2005","journal-title":"Nat. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1038\/ng.955","article-title":"Mutations in BRIP1 confer high risk of ovarian cancer","volume":"43","author":"Rafnar","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Ramus, S.J., Song, H., Dicks, E., Tyrer, J.P., Rosenthal, A.N., Intermaggio, M.P., Fraser, L., Gentry-Maharaj, A., Hayward, J., and Philpott, S. (2015). Germline Mutations in the BRIP1, BARD1, PALB2, and NBN Genes in Women With Ovarian Cancer. J. Natl. Cancer Inst., 107.","DOI":"10.1093\/jnci\/djv214"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"747","DOI":"10.7326\/0003-4819-71-4-747","article-title":"Soft-Tissue Sarcomas, Breast Cancer, and Other Neoplasms","volume":"71","author":"Li","year":"1969","journal-title":"Ann. Intern. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s40291-013-0020-0","article-title":"Tumor protein p53 (TP53) testing and Li-Fraumeni syndrome: Current status of clinical applications and future directions","volume":"17","author":"Sorrell","year":"2013","journal-title":"Mol. Diagn. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1158\/1535-7163.MCT-12-0950","article-title":"RAD51C-Deficient Cancer Cells Are Highly Sensitive to the PARP Inhibitor Olaparib","volume":"12","author":"Min","year":"2013","journal-title":"Mol. Cancer Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.ygyno.2016.08.328","article-title":"In vivo anti-tumor activity of the PARP inhibitor niraparib in homologous recombination deficient and proficient ovarian carcinoma","volume":"143","author":"AlHilli","year":"2016","journal-title":"Gynecol. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"8109","DOI":"10.1158\/0008-5472.CAN-06-0140","article-title":"Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition","volume":"66","author":"McCabe","year":"2006","journal-title":"Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1056\/NEJMoa1911440","article-title":"Olaparib for Metastatic Castration-Resistant Prostate Cancer","volume":"382","author":"Mateo","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1056\/NEJMoa1500596","article-title":"PD-1 Blockade in Tumors with Mismatch-Repair Deficiency","volume":"372","author":"Le","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3753","DOI":"10.1158\/1078-0432.CCR-18-4070","article-title":"FDA Approval Summary: Pembrolizumab for the Treatment of Microsatellite Instability-High Solid Tumors","volume":"25","author":"Marcus","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1093\/bioinformatics\/bty790","article-title":"smCounter2: An accurate low-frequency variant caller for targeted sequencing data with unique molecular identifiers","volume":"35","author":"Xu","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1093\/hmg\/ddu733","article-title":"Comparison and integration of deleteriousness prediction methods for nonsynonymous SNVs in whole exome sequencing studies","volume":"24","author":"Dong","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"D886","DOI":"10.1093\/nar\/gky1016","article-title":"CADD: Predicting the deleteriousness of variants throughout the human genome","volume":"47","author":"Rentzsch","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1093\/bioinformatics\/bty897","article-title":"VarSome: The human genomic variant search engine","volume":"35","author":"Kopanos","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_53","first-page":"5248","article-title":"A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: Development of international criteria for the determination of microsatellite instability in colorectal cancer","volume":"58","author":"Boland","year":"1998","journal-title":"Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.canlet.2009.02.009","article-title":"Mitochondrial genome alterations in rectal and sigmoid carcinomas","volume":"280","author":"Pinheiro","year":"2009","journal-title":"Cancer Lett."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1097\/PAS.0000000000000684","article-title":"Pathologic Findings in Prophylactic and Nonprophylactic Hysterectomy Specimens of Patients With Lynch Syndrome","volume":"40","author":"Bartosch","year":"2016","journal-title":"Am. J. Surg. Pathol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/10\/2834\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:15:24Z","timestamp":1760177724000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/10\/2834"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,30]]},"references-count":55,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["cancers12102834"],"URL":"https:\/\/doi.org\/10.3390\/cancers12102834","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,30]]}}}