{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T18:25:55Z","timestamp":1787595955319,"version":"build-2736575974"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Colombian Ministry of Science, Technology, and Innovation","award":["Program 92191, Project 92268, Contract No. 800-2023"],"award-info":[{"award-number":["Program 92191, Project 92268, Contract No. 800-2023"]}]},{"name":"Fundaci\u00f3n Salud de los Andes"},{"name":"HERMES grants","award":["Nos. 52457, 5607, 53654, and 6641"],"award-info":[{"award-number":["Nos. 52457, 5607, 53654, and 6641"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Triple-negative breast cancer (TNBC) is characterized by aggressive behaviour, high tumor heterogeneity, and an increased likelihood of recurrence and early metastasis. These factors hinder successful treatment. Genetic diagnosis enables personalized clinical recommendations and treatment options. The objective of this study was to validate whole-exome sequencing (WES) and variant prioritization in cancer susceptibility genes (CSG) associated with hereditary cancer (HC) predisposition in TNBC patients (n\u2009=\u200924). We present the development of a reproducible bioinformatic pipeline and its technical validation in a validation cohort (n\u2009=\u200925). This cohort comprised individuals with diverse primary tumors who had a previously confirmed molecular diagnosis of a hereditary cancer syndrome, serving as gold-standard cases to assess the pipeline\u2019s analytical accuracy. We consolidated a comprehensive panel of cancer genes and determined all variants in the TNBC discovery cohort (12.5% of patients), identifying three pathogenic germline variants (gPV) in\n                    <jats:italic>ATM, RAD51D, and BRCA1<\/jats:italic>\n                    . These genes are involved in the molecular pathway of DNA repair by homologous recombination (HRD). Our results demonstrate that the developed bioinformatic pipeline provides reliable genetic diagnosis of cancer predisposition syndromes from exome data, applicable not only to TNBC patients but also to individuals with any cancer suspected of having a hereditary component.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0356762","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T17:38:39Z","timestamp":1787593119000},"page":"e0356762","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exome-based cancer driver gene comprehensive testing can provide a genetic diagnosis for individuals with triple-negative breast cancer"],"prefix":"10.1371","volume":"21","author":[{"given":"Daniel","family":"Alzate","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel Yobany","family":"S\u00e1nchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yovana","family":"Pacheco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Isaza Ruget","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramiro","family":"S\u00e1nchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Castillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6084-8981","authenticated-orcid":true,"given":"Carlos A.","family":"Parra-L\u00f3pez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"issue":"10","key":"pone.0356762.ref001","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1002\/cac2.12358","article-title":"Breast cancer: an up-to-date review and future perspectives","volume":"42","author":"R Hong","year":"2022","journal-title":"Cancer Commun (Lond)"},{"issue":"4","key":"pone.0356762.ref002","article-title":"The nature of triple-negative breast cancer classification and antitumoral strategies","volume":"18","author":"S Kim","year":"2020","journal-title":"Genomics Inform"},{"issue":"4","key":"pone.0356762.ref003","doi-asserted-by":"crossref","first-page":"479","DOI":"10.6004\/jnccn.2020.7554","article-title":"Role of immunotherapy in Triple-Negative Breast Cancer","volume":"18","author":"TE Keenan","year":"2020","journal-title":"J Natl Compr Canc Netw"},{"issue":"11","key":"pone.0356762.ref004","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1016\/j.annonc.2022.07.008","article-title":"Comprehensive cancer predisposition testing within the prospective MASTER trial identifies hereditary cancer patients and supports treatment decisions for rare cancers","volume":"33","author":"A Jahn","year":"2022","journal-title":"Ann Oncol"},{"issue":"12","key":"pone.0356762.ref005","doi-asserted-by":"crossref","first-page":"104360","DOI":"10.1016\/j.ejmg.2021.104360","article-title":"Somatic mosaics in hereditary tumor predisposition syndromes","volume":"64","author":"V Steinke-Lange","year":"2021","journal-title":"Eur J Med Genet"},{"issue":"6","key":"pone.0356762.ref006","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1038\/s41431-025-01814-z","article-title":"Exome-based cancer predisposition gene testing can provide a genetic diagnosis for individuals with heterogeneous tumor phenotypes","volume":"33","author":"S Hini\u0107","year":"2025","journal-title":"Eur J Hum Genet"},{"key":"pone.0356762.ref007","volume-title":"Genomics in the cloud: using docker, GATK, and WDL in Terra","author":"G Auwera","year":"2020","edition":"1"},{"key":"pone.0356762.ref008","unstructured":"Andrews S. 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