{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T13:50:53Z","timestamp":1780494653540,"version":"3.54.1"},"reference-count":78,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"College of Medicine and Medical Sciences, Arabian Gulf University"},{"name":"Royal College of Surgeons in Ireland\u2010Bahrain"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Germline variants in<jats:italic>BRCA1<\/jats:italic>and<jats:italic>BRCA2<\/jats:italic>(<jats:italic>BRCA1\/<\/jats:italic>2) genes are the most common cause of hereditary breast cancer. However, a significant number of cases are not linked to these two genes and additional high-, moderate- and low-penetrance genes have been identified in breast cancer. The advent of next-generation sequencing (NGS) allowed simultaneous sequencing of multiple cancer-susceptibility genes and prompted research in this field. So far, cancer-predisposition genes other than<jats:italic>BRCA1<\/jats:italic>\/<jats:italic>2<\/jats:italic>have not been studied in the population of Bahrain. We performed a targeted NGS using a multi-panel covering 180 genes associated with cancer predisposition to investigate the spectrum and frequency of germline variants in 54 women with a positive personal and\/or family history of breast cancer. Sequencing analysis revealed germline variants in 29 (53.7%) patients. Five pathogenic\/likely pathogenic variants in four DNA repair pathway-related genes were identified in five unrelated patients (9.3%). Two<jats:italic>BRCA1<\/jats:italic>variants, namely the missense variant c.287A&gt;G (p.Asp96Gly) and the truncating variant c.1066C&gt;T (p.Gln356Ter), were detected in two patients (3.7%). Three variants in non-<jats:italic>BRCA1\/2<\/jats:italic>genes were detected in three patients (1.85% each) with a strong family history of breast cancer. These included a monoallelic missense variant c.1187G&gt;A (p.Gly396Asp) in<jats:italic>MUTYH<\/jats:italic>gene, and two truncating variants namely c.3343C&gt;T (p.Arg1115Ter) in<jats:italic>MLH3<\/jats:italic>gene and c.1826G&gt;A (p.Trp609Ter) in<jats:italic>PMS1<\/jats:italic>gene. Other variants of uncertain significance (VUS) were also detected, and some of them were found together with the deleterious variants. In this first application of NGS-based multigene testing in Bahraini women with breast cancer, we show that multigene testing can yield additional genomic information on low-penetrance genes, although the clinical significance of these genes has not been fully appreciated yet. Our findings also provide valuable epidemiological information for future studies and highlight the importance of genetic testing, and an NGS-based multigene analysis may be applied supplementary to traditional genetic counseling.<\/jats:p>","DOI":"10.1371\/journal.pone.0291015","type":"journal-article","created":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T17:23:54Z","timestamp":1693589034000},"page":"e0291015","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Investigation of germline variants in Bahraini women with breast cancer using next-generation sequencing based-multigene panel"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8397-3689","authenticated-orcid":true,"given":"Ghada","family":"Al-Kafaji","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghufran","family":"Jassim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amani","family":"AlHajeri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amna Mohamed Tayeb","family":"Alawadhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam","family":"Fida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Sahin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faisal","family":"Alali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Fadel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,9,1]]},"reference":[{"key":"pone.0291015.ref001","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.breast.2022.08.010","article-title":"Current and future burden of breast cancer: Global statistics for 2020 and 2040","volume":"66","author":"M Arnold","year":"2022","journal-title":"The Breast"},{"key":"pone.0291015.ref002","first-page":"145","article-title":"Hereditary breast cancer: Clinical, pathological and molecular characteristics","volume":"8","author":"MJ Larsen","year":"2014","journal-title":"Breast Cancer (Auckl)"},{"key":"pone.0291015.ref003","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1002\/humu.23406","article-title":"Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations","volume":"39","author":"and EMBRACE, and GEMO Study Collaborators, and HEBON","year":"2018","journal-title":"Hum Mutat"},{"key":"pone.0291015.ref004","unstructured":"Central Intelligence Agency. September 27, 2021 \u2013via CIA.gov."},{"key":"pone.0291015.ref005","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1101\/gr.191478.115","article-title":"Indigenous Arabs are descendants of the earliest split from ancient Eurasian populations","volume":"26","author":"JL Rodriguez-Flores","year":"2016","journal-title":"Genome Res"},{"issue":"1","key":"pone.0291015.ref006","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3109\/03014460.2012.728622","article-title":"Genetic position of Bahrain natives among wider Middle East populations according to Alu insertion polymorphisms","volume":"40","author":"R Bahri","year":"2013","journal-title":"Ann Hum Biol"},{"key":"pone.0291015.ref007","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.gene.2013.09.092","article-title":"United Arab Emirates: phylogenetic relationships and ancestral populations","volume":"533","author":"R Garcia-Bertrand","year":"2014","journal-title":"Gene"},{"key":"pone.0291015.ref008","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1742-4755-6-17","article-title":"Consanguinity and reproductive health among Arabs","volume":"6","author":"GO Tadmouri","year":"2009","journal-title":"Reprod Health"},{"issue":"2","key":"pone.0291015.ref009","first-page":"e176","article-title":"Epidemiology of breast cancer among Bahraini women. Data from the Bahrain Cancer Registry","volume":"14","author":"RR Hamadeh","year":"2014","journal-title":"Sultan Qaboos Univ Med J"},{"issue":"3","key":"pone.0291015.ref010","first-page":"612","article-title":"Association of reproductive factors with the incidence of breast cancer in Gulf Cooperation Council countries","volume":"15","author":"K Ravichandran","year":"2009","journal-title":"EMHJ"},{"key":"pone.0291015.ref011","unstructured":"National Genome Center https:\/\/www.moh.gov.bh\/GenomeProject?lang=en#:~:text=The%20Bahrain%20Genome%20Project%20aims,so%20called%20%E2%80%9Cpersonalized%20medicine%E2%80%9D."},{"key":"pone.0291015.ref012","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1016\/S0140-6736(01)06524-2","article-title":"Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58 209 women with breast cancer and 101 986 women without the disease","volume":"358","author":"Cancer, Collaborative Group on Hormonal Factors in Breast Cancer (CGoHFiB)","year":"2001","journal-title":"The Lancet"},{"key":"pone.0291015.ref013","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s10549-017-4325-2","article-title":"Family history and risk of breast cancer: an analysis accounting for family structure","volume":"165","author":"HR Brewer","year":"2017","journal-title":"Breast Cancer Res Treat"},{"key":"pone.0291015.ref014","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1126\/science.2270482","article-title":"Linkage of early-onset familial breast cancer to chromosome 17q21","volume":"250","author":"JM Hall","year":"1990","journal-title":"Science"},{"key":"pone.0291015.ref015","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1126\/science.8091231","article-title":"Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12\u201313","volume":"265","author":"R Wooster","year":"1994","journal-title":"Science"},{"key":"pone.0291015.ref016","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1086\/301749","article-title":"Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium","volume":"62","author":"D Ford","year":"1998","journal-title":"Am J Hum Genet"},{"key":"pone.0291015.ref017","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1126\/science.1251827","article-title":"Two decades after BRCA: Setting paradigms in personalized cancer care and prevention","volume":"343","author":"FJ Couch","year":"2014","journal-title":"Science"},{"key":"pone.0291015.ref018","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":"KB Kuchenbaecker","year":"2017","journal-title":"JAMA"},{"key":"pone.0291015.ref019","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.pmbts.2017.07.002","article-title":"Breast cancer epidemiology, prevention, and screening","volume":"151","author":"S Winters","year":"2017","journal-title":"Prog Mol Biol Transl Sci"},{"key":"pone.0291015.ref020","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1126\/science.aam7344","article-title":"PARP inhibitors: The first synthetic lethal targeted therapy","volume":"355","author":"CJ Lord","year":"2017","journal-title":"Science"},{"key":"pone.0291015.ref021","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1056\/NEJMoa1802905","article-title":"Talazoparib in patients with advanced breast cancer and a germline BRCA mutation","volume":"379","author":"JK Litton","year":"2018","journal-title":"N Engl J Med"},{"key":"pone.0291015.ref022","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1056\/NEJMoa1706450","article-title":"Olaparib for metastatic breast cancer in patients with a germline BRCA mutation","volume":"377","author":"M Robson","year":"2017","journal-title":"N Engl J Med"},{"key":"pone.0291015.ref023","doi-asserted-by":"crossref","first-page":"2394","DOI":"10.1056\/NEJMoa2105215","article-title":"Adjuvant Olaparib for patients with BRCA1- or BRCA2-mutated breast cancer","volume":"384","author":"AN Tutt","year":"2021","journal-title":"N Engl J Med"},{"key":"pone.0291015.ref024","doi-asserted-by":"crossref","first-page":"674094","DOI":"10.3389\/fgene.2021.674094","article-title":"Characteristics of germline non-BRCA mutation status of high-risk breast cancer patients in China and correlation with high-risk factors and multigene testing suggestions","volume":"12","author":"Y Su","year":"2021","journal-title":"Front Genet"},{"key":"pone.0291015.ref025","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1002\/cam4.1251","article-title":"Optimizing the identification of risk-relevant mutations by multigene panel testing in selected hereditary breast\/ovarian cancer families","volume":"7","author":"A Coppa","year":"2018","journal-title":"Cancer Med"},{"key":"pone.0291015.ref026","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/sj.bjc.6604830","article-title":"Breast cancer risks in women with a family history of breast or ovarian cancer who have tested negative for a BRCA1 or BRCA2 mutation","volume":"100","author":"KA Metcalfe","year":"2009","journal-title":"Br J Cancer"},{"key":"pone.0291015.ref027","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1093\/annonc\/mdv022","article-title":"Genetics of breast cancer: a topic in evolution","volume":"26","author":"S Shiovitz","year":"2015","journal-title":"Ann Oncol"},{"key":"pone.0291015.ref028","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/nrc.2016.72","article-title":"Hereditary breast and ovarian cancer: New genes in confined pathways","volume":"16","author":"FC Nielsen","year":"2016","journal-title":"Nat Rev Cancer"},{"key":"pone.0291015.ref029","doi-asserted-by":"crossref","first-page":"77","DOI":"10.6004\/jnccn.2021.0001","article-title":"Genetic\/familial high-risk assessment: Breast, ovarian, and pancreatic, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology","volume":"19","author":"MB Daly","year":"2021","journal-title":"J Natl Compr Canc Netw"},{"key":"pone.0291015.ref030","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.breast.2019.01.002","article-title":"Decoding hereditary breast cancer\u201d benefits and questions from multigene panel testing","volume":"45","author":"C Colas","year":"2019","journal-title":"The Breast"},{"key":"pone.0291015.ref031","doi-asserted-by":"crossref","first-page":"e0125571","DOI":"10.1371\/journal.pone.0125571","article-title":"Identification of a comprehensive spectrum of genetic factors for hereditary breast cancer in a Chinese population by next-generation sequencing","volume":"10","author":"X Yang","year":"2015","journal-title":"PLoS One"},{"issue":"3","key":"pone.0291015.ref032","doi-asserted-by":"crossref","first-page":"697","DOI":"10.4143\/crt.2019.559","article-title":"Detection of germline mutations in breast cancer patients with clinical features of hereditary cancer syndrome using a multi-gene panel test","volume":"52","author":"HC Shin","year":"2020","journal-title":"Cancer Res Treat"},{"key":"pone.0291015.ref033","doi-asserted-by":"crossref","first-page":"106","DOI":"10.3390\/genes14010106","article-title":"Frequency of pathogenic germline mutations in early and late onset familial breast cancer patients using multi-gene panel sequencing: An Egyptian study","volume":"14","author":"A Nassar","year":"2022","journal-title":"Genes"},{"key":"pone.0291015.ref034","doi-asserted-by":"crossref","first-page":"e00771","DOI":"10.1002\/mgg3.771","article-title":"Characterization of BRCA1 and BRCA2 genetic variants in a cohort of Bahraini breast cancer patients using next-generation sequencing","volume":"7","author":"F Al Hannan","year":"2019","journal-title":"Mol Genet Genom Med"},{"issue":"1","key":"pone.0291015.ref035","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":"MM Li","year":"2017","journal-title":"J Mol Diagn"},{"key":"pone.0291015.ref036","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.ajhg.2017.01.004","article-title":"InterVar: clinical interpretation of genetic variants by the 2015 ACMG-AMP guidelines","volume":"100","author":"Q Li","year":"2017","journal-title":"Am J Hum Genet"},{"issue":"1","key":"pone.0291015.ref037","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1093\/nargab\/lqab122","article-title":"A comparison on predicting functional impact of genomic variants","volume":"4","author":"D Wang","year":"2022","journal-title":"NAR Genom Bioiform"},{"key":"pone.0291015.ref038","doi-asserted-by":"crossref","unstructured":"Bernstein C, Prasad RA, Nfonsam V, Bernstei H. DNA damage, DNA repair and cancer. In new research directions in DNA repair; In Tech Open: London, UK, 2013.","DOI":"10.5772\/53919"},{"key":"pone.0291015.ref039","doi-asserted-by":"crossref","first-page":"10","DOI":"10.3389\/fnut.2015.00010","article-title":"Exploiting base excision repair to improve therapeutic approaches for pancreatic cancer","volume":"2","author":"G Sharbeen","year":"2015","journal-title":"Front Nutr"},{"key":"pone.0291015.ref040","doi-asserted-by":"crossref","first-page":"5584","DOI":"10.1038\/s41467-020-19406-4","article-title":"Pan-cancer landscape of homologous recombination deficiency","volume":"11","author":"L Nguyen","year":"2020","journal-title":"Nat Commun"},{"key":"pone.0291015.ref041","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/s41586-018-0461-z","article-title":"Accurate functional classification of thousands of BRCA1 variants with saturation genome editing","volume":"562","author":"GM Findlay","year":"2018","journal-title":"Nature"},{"key":"pone.0291015.ref042","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s13238-010-0010-5","article-title":"The role of BRCA1 in DNA damage response","volume":"1","author":"J Wu","year":"2010","journal-title":"Protein Cell"},{"key":"pone.0291015.ref043","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1159\/000455999","article-title":"Germline mutations in triple-negative breast cancer","volume":"12","author":"E Hahnena","year":"2017","journal-title":"Breast Care"},{"issue":"12","key":"pone.0291015.ref044","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1002\/cncr.31307","article-title":"PARP Inhibition in BRCA-Mutant Breast Cancer","volume":"124","author":"A. Turk","year":"2018","journal-title":"Cancer"},{"key":"pone.0291015.ref045","doi-asserted-by":"crossref","first-page":"769280","DOI":"10.3389\/fonc.2021.769280","article-title":"Emerging role of PARP inhibitors in metastatic triple negative breast cancer. Current scenario and future perspectives","volume":"11","author":"G Barchiesi","year":"2021","journal-title":"Front Oncol"},{"key":"pone.0291015.ref046","doi-asserted-by":"crossref","first-page":"742139","DOI":"10.3389\/fonc.2021.742139","article-title":"Efficacy and safety of PARP inhibitors in advanced or metastatic triple-negative breast cancer: A systematic review and meta-analysis","volume":"11","author":"X Liu","year":"2021","journal-title":"Front Oncol"},{"key":"pone.0291015.ref047","doi-asserted-by":"crossref","first-page":"543","DOI":"10.2147\/CLEP.S206949","article-title":"A systematic review of the international prevalence of BRCA mutation in breast cancer","volume":"11","author":"N Armstrong","year":"2019","journal-title":"Clin Epidemiol"},{"key":"pone.0291015.ref048","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.cancergen.2022.02.006","article-title":"Evaluation of hereditary\/familial breast cancer patients with multigene targeted next generation sequencing panel and MLPA analysis in Turkey","volume":"262","author":"E Bora","year":"2022","journal-title":"Cancer Genet"},{"issue":"4","key":"pone.0291015.ref049","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.jmoldx.2020.01.013","article-title":"Germline mutation in 1338 BRCA-negative Chinese hereditary breast and\/or ovarian cancer patients","volume":"22","author":"A Kwong","year":"2020","journal-title":"J Mol Diagn"},{"key":"pone.0291015.ref050","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s12920-017-0244-7","article-title":"Next-generation sequencing in familial breast cancer patients from Lebanon","volume":"10","author":"N Jalkh","year":"2017","journal-title":"BMC Med Genom"},{"key":"pone.0291015.ref051","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1002\/ijc.30143","article-title":"Identification of novel BRCA founder mutations in Middle Eastern Breast cancer patients using capture and Sanger sequencing analysis","volume":"139","author":"R Bu","year":"2016","journal-title":"Int J Cancer"},{"key":"pone.0291015.ref052","first-page":"358","article-title":"Genotype and phenotype correlation of breast cancer in BRCA mutation carriers and non-carriers","volume":"9","author":"SM AL Bader","year":"2017","journal-title":"J Cancer Sci Ther"},{"key":"pone.0291015.ref053","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1186\/1897-4287-5-4-199","article-title":"Base excision repair and the role of MUTYH","volume":"5","author":"C Kairupan","year":"2007","journal-title":"Hered Cancer Clin Pract"},{"key":"pone.0291015.ref054","doi-asserted-by":"crossref","first-page":"428","DOI":"10.5306\/wjco.v11.i7.428","article-title":"MUTYH: Not just polyposis","volume":"11","author":"MC Curia","year":"2020","journal-title":"World J Clin Oncol"},{"key":"pone.0291015.ref055","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1056\/NEJMoa025283","article-title":"Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH","volume":"348","author":"OM Sieber","year":"2003","journal-title":"N Engl J Med"},{"key":"pone.0291015.ref056","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1007\/s10549-008-0042-1","article-title":"Mutations of the MYH gene do not substantially contribute to the risk of breast cancer","volume":"114","author":"ME Beiner","year":"2009","journal-title":"Breast Cancer Res Treat"},{"key":"pone.0291015.ref057","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s10689-018-00114-4","article-title":"Monoallelic MUTYH carrier status is not associated with increased breast cancer risk in a multigene panel cohort","volume":"18","author":"K Fulk","year":"2019","journal-title":"Fam Cancer"},{"key":"pone.0291015.ref058","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1002\/cncr.26506","article-title":"MutYH mutation carriers have increased breast cancer risk","volume":"118","author":"G Rennert","year":"2012","journal-title":"Cancer"},{"key":"pone.0291015.ref059","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1007\/s10549-010-0801-7","article-title":"Increased MUTYH mutation frequency among Dutch families with breast cancer and colorectal cancer","volume":"124","author":"M Wasielewski","year":"2010","journal-title":"Breast Cancer Res Treat"},{"issue":"7","key":"pone.0291015.ref060","doi-asserted-by":"crossref","first-page":"8310","DOI":"10.18632\/oncotarget.7027","article-title":"Multiple gene sequencing for risk assessment in patients with early-onset or familial breast cancer","volume":"7","author":"PH Lin","year":"2016","journal-title":"Oncotarget"},{"key":"pone.0291015.ref061","doi-asserted-by":"crossref","first-page":"894358","DOI":"10.3389\/fmed.2022.894358","article-title":"Multi-gene panel testing increases germline predisposing mutaions\u2019 detection in a cohort of breast\/ovarian cancer patients from Southern Italy","volume":"9","author":"M Nunziato","year":"2022","journal-title":"Front Med"},{"key":"pone.0291015.ref062","doi-asserted-by":"crossref","first-page":"2711","DOI":"10.3390\/cancers13112711","article-title":"Study of the genetic variants in brca1\/2 and non-brca genes in a population-based cohort of 2155 breast\/ovary cancer patients, including 443 triple-negative breast cancer patients, in Argentina","volume":"13","author":"AR Solano","year":"2021","journal-title":"Cancers"},{"key":"pone.0291015.ref063","doi-asserted-by":"crossref","first-page":"548","DOI":"10.3390\/jpm11060548","article-title":"Prevalence and clinicopathological characteristics of moderate and high- penetrance genes in non-BRCA1\/2 breast cancer high-risk Spanish families","volume":"11","author":"M Fonfria","year":"2021","journal-title":"J Pers Med"},{"key":"pone.0291015.ref064","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.dnarep.2006.11.001","article-title":"MUTYH-associated polyposis\u2014from defect in base excision repair to clinical genetic testing","volume":"6","author":"JP Cheadle","year":"2007","journal-title":"DNA Repair (Amst)"},{"key":"pone.0291015.ref065","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/nrm1907","article-title":"The multifaceted mismatch-repair system","volume":"7","author":"J. Jiricny","year":"2006","journal-title":"Nat Rev Mol Cell Biol"},{"key":"pone.0291015.ref066","doi-asserted-by":"crossref","first-page":"122","DOI":"10.3389\/fmolb.2020.00122","article-title":"Mismatch repair pathway, genome stability and cancer","volume":"7","author":"N Pecina-\u0160laus","year":"2020","journal-title":"Front Mol Biosci"},{"key":"pone.0291015.ref067","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1200\/JCO.2011.39.5590","article-title":"Colorectal and other cancer risks for carriers and noncarriers from families with a DNA mismatch repair gene mutation: a prospective cohort study","volume":"14","author":"AK Win","year":"2012","journal-title":"J Clin Oncol"},{"issue":"10","key":"pone.0291015.ref068","doi-asserted-by":"crossref","first-page":"e1003869","DOI":"10.1371\/journal.pgen.1003869","article-title":"Dominant mutations in S. cerevisiae PMS1 identify the Mlh1\u2010Pms1 endonuclease active site and an exonuclease 1\u2010independent mismatch repair pathway","volume":"9","author":"CE Smith","year":"2013","journal-title":"PLoS Genet"},{"key":"pone.0291015.ref069","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/s10689-004-7993-0","article-title":"Lynch syndrome genes","volume":"4","author":"P. Peltomali","year":"2005","journal-title":"Familial Cancer"},{"issue":"3","key":"pone.0291015.ref070","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1038\/s41436-019-0694-8","article-title":"Evaluating the role of MLH3 p.Ser1188Ter variant in inherited breast cancer predisposition","volume":"22","author":"S Koivuluoma","year":"2020","journal-title":"Genet Med"},{"key":"pone.0291015.ref071","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1111\/cas.14242","article-title":"Prevalence of hereditary breast and ovarian cancer (HBOC) predisposition gene mutations among 882 HBOC high-risk Chinese individuals","volume":"111","author":"D Shao","year":"2020","journal-title":"Cancer Sci"},{"key":"pone.0291015.ref072","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/gcc.22911","article-title":"Analysis of 11 candidate genes in 849 adult patients with suspected hereditary cancer predisposition","volume":"60","author":"M Cavaill\u00e9","year":"2021","journal-title":"Genes Chromosomes Cancer"},{"key":"pone.0291015.ref073","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/s41523-022-00417-x","article-title":"Clinical relevance of pathogenic germline variants in mismatch repair genes in Chinese breast cancer patients","volume":"8","author":"L Hu","year":"2022","journal-title":"NPJ Breast Cancer"},{"key":"pone.0291015.ref074","doi-asserted-by":"crossref","first-page":"580","DOI":"10.18632\/oncotarget.28457","article-title":"Investigating the prevalence of pathogenic variants in Saudi Arabian patients with familial cancer using a multigene next generation sequencing panel","volume":"14","author":"M AlHarbi","year":"2023","journal-title":"Oncotarget"},{"key":"pone.0291015.ref075","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.1016\/j.sjbs.2020.05.047","article-title":"Targeted sequencing of crucial cancer causing genes of breast cancer in Saudi patients","volume":"27","author":"M Alanazi","year":"2020","journal-title":"Saudi J Biol Sci"},{"key":"pone.0291015.ref076","first-page":"2601","article-title":"A comparative analysis of breast and ovarian cancer-related gene mutations in Canadian and Saudi Arabian patients with breast cancer","volume":"35","author":"Y Amemiya","year":"2015","journal-title":"Anticancer Res"},{"key":"pone.0291015.ref077","doi-asserted-by":"crossref","first-page":"119e124","DOI":"10.1016\/j.breast.2020.07.005","article-title":"Clinicopathological characteristics of gene-positive breast cancer in the United Arab Emirates","volume":"53","author":"A Altinoz","year":"2020","journal-title":"The Breast"},{"key":"pone.0291015.ref078","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3390\/jpm9010015","article-title":"Genetic testing to guide risk-stratified screens for breast cancer","volume":"9","author":"A Willoughby","year":"2019","journal-title":"J Pers Med"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0291015","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T21:22:29Z","timestamp":1703107349000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0291015"}},"subtitle":[],"editor":[{"given":"Amy McCart","family":"Reed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,9,1]]},"references-count":78,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,9,1]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0291015","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,1]]}}}