{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:11:41Z","timestamp":1792642301641,"version":"4.5.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T00:00:00Z","timestamp":1649376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014805","name":"Roche Italia","doi-asserted-by":"publisher","award":["277\/20"],"award-info":[{"award-number":["277\/20"]}],"id":[{"id":"10.13039\/100014805","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Tumour testing of the <jats:italic>BRCA1\/2<\/jats:italic> genes is routinely performed in patients with different cancer histological subtypes. To accurately identify patients with tumour-detected germline pathogenic variants (PVs) is a relevant issue currently under investigation. This study aims at evaluating the performance of the tumour-to-germline diagnostic flowchart model defined at our Institutional Molecular Tumour Board (MTB). Results from tumour BRCA sequencing of 641 consecutive unselected cancer patients were discussed during weekly MTB meetings with the early involvement of clinical geneticists for appropriate referral to genetic counselling. The overall tumour detection rate of <jats:italic>BRCA1\/2<\/jats:italic> PVs was 8.7% (56\/641), ranging from 24.4% (31\/127) in high-grade ovarian cancer to 3.9% (12\/304) in tumours not associated with germline <jats:italic>BRCA1\/2<\/jats:italic> PVs. Thirty-seven patients with PVs (66%) were evaluated by a clinical geneticist, and in 24 of them (64.9%), germline testing confirmed the presence of the PV in blood. Nine of these patients (37.5%) were not eligible for germline testing according to the criteria in use at our institution. Cascade testing was subsequently performed on 18 relatives. The tumour-to-germline diagnostic pipeline, developed in the framework of our institutional MTB, compared with guideline-based germline testing following genetic counselling, proved to be effective in identifying a higher number of germline BRCA PVs carriers.<\/jats:p>","DOI":"10.3389\/fonc.2022.857515","type":"journal-article","created":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T11:32:26Z","timestamp":1649417546000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Management of BRCA Tumour Testing in an Integrated Molecular Tumour Board Multidisciplinary Model"],"prefix":"10.3389","volume":"12","author":[{"given":"Jacopo","family":"Azzollini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Vingiani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Agnelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Tamborini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Perrone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Conca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iolanda","family":"Capone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adele","family":"Busico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Peissel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Rosina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Ducceschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Mantiero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Lopez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Raspagliesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Niger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Duca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Damian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Proto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"de Braud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giancarlo","family":"Pruneri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siranoush","family":"Manoukian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.32074\/1591-951X-324","article-title":"Real-World Data on NGS Diagnostics: A Survey From the Italian Society of Pathology (SIAPeC) NGS Network","volume":"113","author":"Marchetti","year":"2021","journal-title":"Pathologica"},{"key":"B2","doi-asserted-by":"publisher","first-page":"10931","DOI":"10.3390\/ijms222010931","article-title":"Cancer Therapy Guided by Mutation Tests: Current Status and Perspectives","volume":"22","author":"Aleksakhina","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e000094","DOI":"10.1136\/esmoopen-2016-000094","article-title":"Integrating Next-Generation Sequencing Into Clinical Oncology: Strategies, Promises and Pitfalls","volume":"1","author":"Horak","year":"2016","journal-title":"ESMO Open"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4333","article-title":"Mutational Landscape of Metastatic Cancer Revealed From Prospective Clinical Sequencing of 10,000 Patients","volume":"23","author":"Zehir","year":"2017","journal-title":"Nat Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.12.015","article-title":"Implementing Genome-Driven Oncology","volume":"168","author":"Hyman","year":"2017","journal-title":"Cell"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-0015","article-title":"Germline Analysis From Tumor-Germline Sequencing Dyads to Identify Clinically Actionable Secondary Findings","volume":"22","author":"Seifert","year":"2016","journal-title":"Clin Cancer Res"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.11137","article-title":"Mutation Detection in Patients With Advanced Cancer by Universal Sequencing of Cancer-Related Genes in Tumor and Normal DNA vs Guideline-Based Germline Testing","volume":"318","author":"Mandelker","year":"2017","journal-title":"JAMA"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.03.039","article-title":"Pathogenic Germline Variants in 10,389 Adult Cancers","volume":"173","author":"Huang","year":"2018","journal-title":"Cell"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2015.5208","article-title":"Germline Variants in Targeted Tumor Sequencing Using Matched Normal DNA","volume":"2","author":"Schrader","year":"2016","journal-title":"JAMA Oncol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1093\/annonc\/mdw018","article-title":"Incidental Germline Variants in 1000 Advanced Cancers on a Prospective Somatic Genomic Profiling Protocol","volume":"27","author":"Meric-Bernstam","year":"2016","journal-title":"Ann Oncol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2020.6252","article-title":"Comparison of Universal Genetic Testing vs Guideline-Directed Targeted Testing for Patients With Hereditary Cancer Syndrome","volume":"7","author":"Samadder","year":"2021","journal-title":"JAMA Oncol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1093\/jncics\/pkaa018","article-title":"Genetic Counseling and Germline Testing in the Era of Tumor Sequencing: A Cohort Study","volume":"4","author":"Klek","year":"2020","journal-title":"JNCI Cancer Spectr"},{"key":"B13","doi-asserted-by":"publisher","first-page":"4344","DOI":"10.3390\/cancers13174344","article-title":"Implementation of Multigene Germline and Parallel Somatic Genetic Testing in Epithelial Ovarian Cancer: SIGNPOST Study","volume":"13","author":"Chandrasekaran","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2021.7044","article-title":"The Future of Parallel Tumor and Germline Genetic Testing: Is There a Role for All Patients With Cancer","volume":"19","author":"Liu","year":"2021","journal-title":"J Natl Compr Canc Netw"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2018.05.005","article-title":"Validation and Implementation of BRCA1\/2 Variant Screening in Ovarian Tumor Tissue","volume":"20","author":"de Jonge","year":"2018","journal-title":"J Mol Diagn"},{"key":"B16","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1136\/jclinpath-2020-206840","article-title":"Ligurian BRCA Working Group. Implementing NGS-Based BRCA Tumour Tissue Testing in FFPE Ovarian Carcinoma Specimens: Hints From a Real-Life Experience Within the Framework of Expert Recommendations","volume":"74","author":"Rivera","year":"2021","journal-title":"J Clin Pathol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"565","DOI":"10.3390\/diagnostics11030565","article-title":"The Prognostic and Predictive Role of Somatic BRCA Mutations in Ovarian Cancer: Results From a Multicenter Cohort Study","volume":"11","author":"Toss","year":"2021","journal-title":"Diagnostics (Basel)"},{"key":"B18","unstructured":"Foundation Medicine: FoundationOne CDx"},{"key":"B19","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.ejim.2016.03.010","article-title":"Mutation Detection Rates Associated With Specific Selection Criteria for BRCA1\/2 Testing in 1854 High-Risk Families: A Monocentric Italian Study","volume":"32","author":"Azzollini","year":"2016","journal-title":"Eur J Intern Med"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz136","article-title":"Germline-Focussed Analysis of Tumour-Only Sequencing: Recommendations From the ESMO Precision Medicine Working Group","volume":"30","author":"Mandelker","year":"2019","journal-title":"Ann Oncol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(21)00531-3","article-title":"Maintenance Olaparib for Patients With Newly Diagnosed Advanced Ovarian Cancer and a BRCA Mutation (SOLO1\/GOG 3004): 5-Year Follow-Up of a Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial","volume":"22","author":"Banerjee","year":"2021","journal-title":"Lancet Oncol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e194428","DOI":"10.1001\/jamanetworkopen.2019.4428","article-title":"Evaluation of Cancer-Based Criteria for Use in Mainstream BRCA1 and BRCA2 Genetic Testing in Patients With Breast Cancer","volume":"2","author":"Kemp","year":"2019","journal-title":"JAMA Netw Open"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-021-01262-2","article-title":"Uptake and Acceptability of a Mainstreaming Model of Hereditary Cancer Multigene Panel Testing Among Patients With Ovarian, Pancreatic, and Prostate Cancer","volume":"23","author":"Hamilton","year":"2021","journal-title":"Genet Med"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.27.2997","article-title":"Somatic Mutations in BRCA1 and BRCA2 Could Expand the Number of Patients That Benefit From Poly (ADP Ribose) Polymerase Inhibitors in Ovarian Cancer","volume":"28","author":"Hennessy","year":"2010","journal-title":"J Clin Oncol"},{"key":"B25","doi-asserted-by":"publisher","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":"2014","journal-title":"Clin Cancer Res"},{"key":"B26","doi-asserted-by":"publisher","first-page":"pkz028","DOI":"10.1093\/jncics\/pkz028","article-title":"Insights Into BRCA Cancer Predisposition From Integrated Germline and Somatic Analyses in 7632 Cancers","volume":"3","author":"Yost","year":"2019","journal-title":"JNCI Cancer Spectr"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djz080","article-title":"Universal Tumor DNA BRCA1\/2 Testing of Ovarian Cancer: Prescreening PARPi Treatment and Genetic Predisposition","volume":"112","author":"Vos","year":"2020","journal-title":"J Natl Cancer Inst"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1136\/esmoopen-2020-000682","article-title":"Molecular Profile of BRCA-Mutated Biliary Tract Cancers","volume":"5","author":"Spizzo","year":"2020","journal-title":"ESMO Open"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1200\/PO.21.00279","article-title":"Germline Testing Data Validate Inferences of Mutational Status for Variants Detected From Tumor-Only Sequencing","volume":"5","author":"Jalloul","year":"2021","journal-title":"JCO Precis Oncol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1200\/PO.20.00069","article-title":"BRCA Mutations, Homologous DNA Repair Deficiency, Tumor Mutational Burden, and Response to Immune Checkpoint Inhibition in Recurrent Ovarian Cancer","volume":"4","author":"Liu","year":"2020","journal-title":"JCO Precis Oncol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"6421205","DOI":"10.1155\/2020\/6421205","article-title":"Mucinous Histology, BRCA1\/2 Mutations, and Elevated Tumor Mutational Burden in Colorectal Cancer","volume":"2020","author":"Harpaz","year":"2020","journal-title":"J Oncol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1186\/1471-2164-15-516","article-title":"Evaluation and Optimisation of Indel Detection Workflows for Ion Torrent Sequencing of the BRCA1 and BRCA2 Genes","volume":"15","author":"Yeo","year":"2014","journal-title":"BMC Genomics"},{"key":"B33","doi-asserted-by":"publisher","first-page":"542541","DOI":"10.1155\/2014\/542541","article-title":"Genetic Testing in Hereditary Breast and Ovarian Cancer Using Massive Parallel Sequencing","volume":"2014","author":"Ruiz","year":"2014","journal-title":"BioMed Res Int"},{"key":"B34","doi-asserted-by":"publisher","first-page":"5623089","DOI":"10.1155\/2016\/5623089","article-title":"Improved Efficiency and Reliability of NGS Amplicon Sequencing Data Analysis for Genetic Diagnostic Procedures Using AGSA Software","volume":"2016","author":"Poulet","year":"2016","journal-title":"BioMed Res Int"},{"key":"B35","article-title":"Acquired Multiple Secondary BRCA2 Mutations Upon PARPi Resistance in a Metastatic Pancreatic Cancer Patient Harboring a BRCA2 Germline Mutation","volume":"12","author":"Tao","year":"2020","journal-title":"Am J Transl Res"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.10.470","article-title":"Forment J.V. A Meta-Analysis of Reversion Mutations in BRCA Genes Identifies Signatures of DNA End-Joining Repair Mechanisms Driving Therapy Resistance","volume":"32","author":"Tobalina","year":"2021","journal-title":"Ann Oncol"},{"key":"B37","doi-asserted-by":"publisher","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":"B38","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds308","article-title":"Constitutive Promoter Methylation of BRCA1 and RAD51C in Patients With Familial Ovarian Cancer and Early-Onset Sporadic Breast Cancer","volume":"21","author":"Hansmann","year":"2012","journal-title":"Hum Mol Genet"},{"key":"B39","doi-asserted-by":"publisher","first-page":"58","DOI":"10.3390\/cancers11010058","article-title":"Constitutive BRCA1 Promoter Hypermethylation Can Be a Predisposing Event in Isolated Early-Onset Breast Cancer","volume":"11","author":"Azzollini","year":"2019","journal-title":"Cancers (Basel)"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2005936","article-title":"A Population-Based Study of Genes Previously Implicated in Breast Cancer","volume":"384","author":"Hu","year":"2021","journal-title":"N Engl J Med"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1913948","article-title":"Breast Cancer Risk Genes - Association Analysis in More Than 113,000 Women","volume":"384","author":"Dorling","year":"2021","journal-title":"N Engl J Med"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1038\/s41467-020-20496-3","article-title":"A Case-Only Study to Identify Genetic Modifiers of Breast Cancer Risk for BRCA1\/BRCA2 Mutation Carriers","volume":"12","author":"Coignard","year":"2021","journal-title":"Nat Commun"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.857515\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T11:32:32Z","timestamp":1649417552000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.857515\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,8]]},"references-count":42,"alternative-id":["10.3389\/fonc.2022.857515"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2022.857515","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,8]]},"article-number":"857515"}}