{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T20:48:40Z","timestamp":1771274920585,"version":"3.50.1"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T00:00:00Z","timestamp":1660176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["RF-2010-23183729"],"award-info":[{"award-number":["RF-2010-23183729"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003852","name":"Regione Campania","doi-asserted-by":"publisher","award":["CIRO"],"award-info":[{"award-number":["CIRO"]}],"id":[{"id":"10.13039\/501100003852","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003852","name":"Regione Campania","doi-asserted-by":"publisher","award":["SATIN 2014\/2020"],"award-info":[{"award-number":["SATIN 2014\/2020"]}],"id":[{"id":"10.13039\/501100003852","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003852","name":"Regione Campania","doi-asserted-by":"publisher","award":["752\/2019"],"award-info":[{"award-number":["752\/2019"]}],"id":[{"id":"10.13039\/501100003852","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003852","name":"Regione Campania","doi-asserted-by":"publisher","award":["38\/2020"],"award-info":[{"award-number":["38\/2020"]}],"id":[{"id":"10.13039\/501100003852","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Breast cancer is the most common neoplasia in females worldwide, about 10% being hereditary\/familial and due to DNA variants in cancer-predisposing genes, such as the highly penetrant <jats:italic>BRCA1\/BRCA2<\/jats:italic> genes. However, their variants explain up to 25% of the suspected hereditary\/familial cases. The availability of NGS methodologies has prompted research in this field. With the aim to improve the diagnostic sensitivity of molecular testing, a custom designed panel of 44 genes, including also non-coding regions and 5\u2019 and 3\u2019 UTR regions, was set up. Here, are reported the results obtained in a cohort of 64 patients, including also few males, from Southern Italy. All patients had a positive personal and\/or familial history for breast and other cancers, but tested negative to routine <jats:italic>BRCA<\/jats:italic> analysis. After obtaining their written informed consent, a genomic DNA sample\/patient was used to obtain an enriched DNA library, then analyzed by NGS. Sequencing data analysis allowed the identification of pathogenic variants in 12 of tested patients (19%). Interestingly, <jats:italic>MUTYH<\/jats:italic> was the most frequently altered gene, followed by <jats:italic>RNASEL, ATM, MSH6, MRE11A<\/jats:italic>, and <jats:italic>PALB2<\/jats:italic> genes. The reported resultsreinforce the need for enlarged molecular testing beyond <jats:italic>BRCA<\/jats:italic> genes, at least in patients with a personal and familial history, strongly suggestive for a hereditary\/familial form. This gives also a hint to pursue more specific precision oncology therapy.<\/jats:p>","DOI":"10.3389\/fmed.2022.894358","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T06:23:57Z","timestamp":1660199037000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Multi-gene panel testing increases germline predisposing mutations\u2019 detection in a cohort of breast\/ovarian cancer patients from Southern Italy"],"prefix":"10.3389","volume":"9","author":[{"given":"Marcella","family":"Nunziato","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Di Maggio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matilde","family":"Pensabene","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Valeria","family":"Esposito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavio","family":"Starnone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmine","family":"De Angelis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Calabrese","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimiliano","family":"D\u2019Aiuto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerardo","family":"Botti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabino","family":"De Placido","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria","family":"D\u2019Argenio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Salvatore","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1158\/1055-9965.EPI-18-1169","article-title":"Current prevalence of major cancer risk factors and screening test use in the United States: Disparities by education and race\/ethnicity.","volume":"28","author":"Sauer","year":"2019","journal-title":"Cancer Epidemiol Biomarkers Prev."},{"key":"B2","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1007\/s13193-019-01021-5","article-title":"Male breast cancer: current trends\u2014A tertiary care centre experience.","volume":"11","author":"Shah","year":"2020","journal-title":"Indian J Surg Oncol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2177","DOI":"10.7314\/APJCP.2015.16.6.2177","article-title":"The spectrum of genetic mutations in breast cancer.","volume":"16","author":"Sheikh","year":"2015","journal-title":"Asian Pacific J Cancer Prev."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e879","DOI":"10.1002\/mgg3.879","article-title":"The role of BRCA1\/2 in hereditary and familial breast and ovarian cancers.","volume":"7","author":"Hawsawi","year":"2019","journal-title":"Mol Genet Genomic Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1186\/s12885-018-4229-5","article-title":"Germline breast cancer susceptibility gene mutations and breast cancer outcomes.","volume":"18","author":"Wang","year":"2018","journal-title":"BMC Cancer."},{"key":"B6","doi-asserted-by":"publisher","first-page":"3442","DOI":"10.3390\/ijms20143442","article-title":"BRCA1 and BRCA2 testing through next generation sequencing in a small cohort of Italian breast\/ovarian cancer patients: Novel pathogenic and unknown clinical significance variants.","volume":"20","author":"Concolino","year":"2019","journal-title":"Int J Mol Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1007\/978-3-319-70197-4_8","article-title":"Multi-gene panel testing in breast cancer management.","volume":"173","author":"Fountzilas","year":"2018","journal-title":"Cancer Treat Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"220","DOI":"10.15386\/mpr-1083","article-title":"Multi gene panel testing for hereditary breast cancer - Is it ready to be used?.","volume":"92","author":"Catana","year":"2019","journal-title":"Med Pharm Rep."},{"key":"B9","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.aca.2018.09.032","article-title":"A multi-gene panel beyond BRCA1\/BRCA2 to identify new breast cancer-predisposing mutations by a picodroplet PCR followed by a next-generation sequencing strategy: A pilot study.","volume":"1046","author":"Nunziato","year":"2018","journal-title":"Anal Chim Acta."},{"key":"B10","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/j.cca.2015.03.045","article-title":"The molecular analysis of BRCA1 and BRCA2: Next-generation sequencing supersedes conventional approaches.","volume":"446","author":"D\u2019Argenio","year":"2015","journal-title":"Clin Chim Acta."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.2147\/TACG.S245021","article-title":"Challenges of genomic testing for hereditary breast and ovarian cancers.","volume":"14","author":"McAlarnen","year":"2021","journal-title":"Appl Clin Genet."},{"key":"B12","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s12920-019-0652-y","article-title":"Germline variants in DNA repair genes associated with hereditary breast and ovarian cancer syndrome: Analysis of a 21 gene panel in the Brazilian population.","volume":"13","author":"Da Costa","year":"2020","journal-title":"BMC Med Genomics."},{"key":"B13","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/s10689-017-0004-z","article-title":"A multi-gene panel study in hereditary breast and ovarian cancer in Colombia.","volume":"17","author":"Cock-Rada","year":"2018","journal-title":"Fam Cancer."},{"key":"B14","doi-asserted-by":"publisher","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":"Shin","year":"2020","journal-title":"Cancer Res Treat."},{"key":"B15","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1186\/s12885-015-1224-y","article-title":"Development and analytical validation of a 25-gene next generation sequencing panel that includes the BRCA1 and BRCA2 genes to assess hereditary cancer risk.","volume":"15","author":"Judkins","year":"2015","journal-title":"BMC Cancer."},{"key":"B16","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/s10549-018-4661-x","article-title":"Germline deleterious mutations in genes other than BRCA2 are infrequent in male breast cancer.","volume":"169","author":"Fostira","year":"2018","journal-title":"Breast Cancer Res Treat."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1177\/2047487320934265","article-title":"Yield and clinical significance of genetic screening in elite and amateur athletes.","volume":"28","author":"Limongelli","year":"2020","journal-title":"Eur J Prev Cardiol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"e0182272","DOI":"10.1371\/journal.pone.0182272","article-title":"Optimized detection of insertions\/deletions (INDELs) in whole-exome sequencing data.","volume":"12","author":"Kim","year":"2017","journal-title":"PLoS One."},{"key":"B19","doi-asserted-by":"publisher","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":"B20","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1007\/s10549-018-05124-5","article-title":"Prevalence and characterization of ATM germline mutations in Chinese BRCA1\/2-negative breast cancer patients.","volume":"174","author":"Yang","year":"2019","journal-title":"Breast Cancer Res Treat."},{"key":"B22","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1158\/1940-6207.CAPR-20-0448","article-title":"Germline pathogenic variants in the ataxia telangiectasia mutated (ATM) gene are associated with high and moderate risks for multiple cancers.","volume":"14","author":"Hall","year":"2021","journal-title":"Cancer Prev Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1186\/s12885-018-4028-z","article-title":"Is RNASEL: P.Glu265* a modifier of early-onset breast cancer risk for carriers of high-risk mutations?","volume":"18","author":"Nguyen-Dumont","year":"2018","journal-title":"BMC Cancer."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.1016\/j.dnarep.2009.09.009.Adenine","article-title":"Adenine removal activity and bacterial complementation with the human MutY homologue (MUTYH) and Y165C, G382D, P391L and Q324R variants associated with colorectal cancer.","volume":"8","author":"Kundu","year":"2009","journal-title":"DNA Repair."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/bs.pmbts.2017.07.002","article-title":"Breast cancer epidemiology, prevention, and screening.","volume":"151","author":"Winters","year":"2017","journal-title":"Prog Mol Biol Transl Sci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1126\/science.aam7344.PARP","article-title":"PARP inhibitors: The first synthetic lethal targeted therapy.","volume":"355","author":"Lord","year":"2017","journal-title":"Science."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1586\/14737159.2015.1081059","article-title":"Clinical impact on ovarian cancer patients of massive parallel sequencing for BRCA mutation detection: The experience at Gemelli hospital and a literature review.","volume":"15","author":"Minucci","year":"2015","journal-title":"Expert Rev Mol Diagn."},{"key":"B28","doi-asserted-by":"publisher","first-page":"S10","DOI":"10.1038\/ejhg.2016.94","article-title":"New challenges for BRCA testing: A view from the diagnostic laboratory.","volume":"24","author":"Wallace","year":"2016","journal-title":"Eur J Hum Genet."},{"key":"B29","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1038\/gim.2015.166","article-title":"Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing.","volume":"18","author":"Susswein","year":"2016","journal-title":"Genet Med."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.1002\/cncr.30498","article-title":"A study of over 35,000 women with breast cancer tested with a 25-gene panel of hereditary cancer genes.","volume":"123","author":"Buys","year":"2017","journal-title":"Cancer."},{"key":"B31","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1002\/cncr.29010","article-title":"Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel.","volume":"121","author":"Tung","year":"2015","journal-title":"Cancer."},{"key":"B32","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1001\/jamaoncol.2015.2690","article-title":"Clinical actionability of multigene panel testing for hereditary breast and ovarian cancer risk assessment.","volume":"1","author":"Desmond","year":"2015","journal-title":"JAMA Oncol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/j.jmoldx.2015.04.009","article-title":"A systematic comparison of traditional and multigene panel testing for hereditary breast and ovarian cancer genes in more than 1000 patients.","volume":"17","author":"Lincoln","year":"2015","journal-title":"J Mol Diagn."},{"key":"B34","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1200\/JCO.18.01631","article-title":"Underdiagnosis of hereditary breast cancer: Are genetic testing guidelines a tool or an obstacle?.","volume":"37","author":"Beitsch","year":"2019","journal-title":"J Clin Oncol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"380","DOI":"10.6004\/jnccn.2020.0017","article-title":"Genetic\/familial high-risk assessment: Breast, ovarian, and pancreatic, version 1.2020 featured updates to the NCCN guidelines.","volume":"18","author":"Daly","year":"2020","journal-title":"J Natl Compr Cancer Netw."},{"key":"B36","doi-asserted-by":"publisher","first-page":"649435","DOI":"10.3389\/fonc.2021.649435","article-title":"Whole exome sequencing in BRCA1-2 candidate families: The contribution of other cancer susceptibility genes.","volume":"11","author":"Doddato","year":"2021","journal-title":"Front Oncol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1002\/gepi.21971.Penetrance","article-title":"Penetrance of ATM gene mutations in breast cancer: A meta-analysis of different measures of risk.","volume":"40","author":"Marabelli","year":"2016","journal-title":"Genet Epidemiol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"440","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":"B39","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1056\/nejmoa1913948","article-title":"Breast cancer risk genes \u2014 Association analysis in more than 113,000 women.","volume":"384","author":"Dorling","year":"2021","journal-title":"N Engl J Med."},{"key":"B40","doi-asserted-by":"publisher","first-page":"18302","DOI":"10.1074\/jbc.M109.016717","article-title":"PALB2 regulates recombinational repair through chromatin association and oligomerization.","volume":"284","author":"Sy","year":"2009","journal-title":"J Biol Chem."},{"key":"B41","doi-asserted-by":"publisher","first-page":"7353","DOI":"10.1158\/0008-5472.CAN-10-1012","article-title":"PALB2\/FANCN: Recombining cancer and fanconi anemia.","volume":"70","author":"Tischkowitz","year":"2010","journal-title":"Cancer Res."},{"key":"B42","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.breastdis.2015.07.017","article-title":"Breast-cancer risk in families with mutations in PALB2.","volume":"26","author":"Thomas","year":"2015","journal-title":"Breast Dis."},{"key":"B43","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/nrc3878","article-title":"Milestones of Lynch syndrome: 1895-2015.","volume":"15","author":"Lynch","year":"2015","journal-title":"Nat Rev Cancer."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1038\/gim.2017.254.MSH6","article-title":"MSH6 and PMS2 germ-line pathogenic variants implicated in Lynch syndrome are associated with breast cancer.","volume":"20","author":"Roberts","year":"2018","journal-title":"Genet Med."},{"key":"B45","doi-asserted-by":"publisher","first-page":"7154","DOI":"10.1093\/nar\/gkab492","article-title":"Structure of the mammalian adenine DNA glycosylase MUTYH: Insights into the base excision repair pathway and cancer.","volume":"49","author":"Nakamura","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"B46","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.dnarep.2006.11.001","article-title":"MUTYH-associated polyposis-From defect in base excision repair to clinical genetic testing.","volume":"6","author":"Cheadle","year":"2007","journal-title":"DNA Repair."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1875","DOI":"10.1038\/sj.bjc.6605966","article-title":"A large-scale meta-analysis to refine colorectal cancer risk estimates associated with MUTYH variants.","volume":"103","author":"Theodoratou","year":"2010","journal-title":"Br J Cancer."},{"key":"B48","doi-asserted-by":"publisher","first-page":"428","DOI":"10.5306\/wjco.v11.i7.428","article-title":"MUTYH: Not just polyposis.","volume":"11","author":"Curia","year":"2020","journal-title":"World J Clin Oncol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1557","DOI":"10.1002\/ijc.30197","article-title":"Risk of extracolonic cancers for people with biallelic and monoallelic mutations in MUTYH.","volume":"139","author":"Win","year":"2016","journal-title":"Int J Cancer."},{"key":"B50","doi-asserted-by":"publisher","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":"Wasielewski","year":"2010","journal-title":"Breast Cancer Res Treat."},{"key":"B51","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1158\/1055-9965.EPI-05-0653","article-title":"Genetic polymorphisms in base-excision repair pathway genes and risk of breast cancer.","volume":"15","author":"Zhang","year":"2006","journal-title":"Cancer Epidemiol Biomarkers Prev."},{"key":"B52","doi-asserted-by":"publisher","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":"Beiner","year":"2009","journal-title":"Breast Cancer Res Treat."},{"key":"B53","doi-asserted-by":"publisher","first-page":"2256","DOI":"10.1007\/bf02236735","article-title":"Cancer risks for monoallelic MUTYH mutation carriers with a family history of colorectal cancer.","volume":"129","author":"Win","year":"2011","journal-title":"Int J Cancer."},{"key":"B54","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1007\/s10549-012-1965-0","article-title":"MUTYH gene variants and breast cancer in a Dutch case-control study.","volume":"134","author":"Out","year":"2012","journal-title":"Breast Cancer Res Treat."},{"key":"B55","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/bs.acr.2021.03.003","article-title":"Unraveling the genomic landscape of colorectal cancer through mutational signatures.","volume":"151","author":"D\u00edaz-Gay","year":"2021","journal-title":"Adv Cancer Res."},{"key":"B56","doi-asserted-by":"publisher","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":"Solano","year":"2021","journal-title":"Cancers."},{"key":"B57","doi-asserted-by":"publisher","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":"Fonfria","year":"2021","journal-title":"J Pers Med."},{"key":"B58","author":"Boffetta","year":"2019","journal-title":"Module in Biomedical Sciences - Encyclopedia of Cancer."},{"key":"B59","doi-asserted-by":"publisher","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":"Sharbeen","year":"2015","journal-title":"Front Nutr."},{"key":"B60","doi-asserted-by":"publisher","first-page":"583","DOI":"10.3389\/fonc.2018.00583","article-title":"Contribution of MUtYH variants to male breast cancer risk: Results from a multicenter study in Italy.","volume":"8","author":"Rizzolo","year":"2018","journal-title":"Front Oncol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1086\/340450","article-title":"Germline alterations of the RNASEL gene, a candidate HPC1 gene at 1q25, in patients and families with prostate cancer.","volume":"70","author":"R\u00f6kman","year":"2002","journal-title":"Am J Hum Genet."},{"key":"B62","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1002\/ijc.21254","article-title":"RNASEL germline variants are associated with pancreatic cancer.","volume":"117","author":"Bartsch","year":"2005","journal-title":"Int J Cancer."},{"key":"B63","doi-asserted-by":"publisher","first-page":"e2492","DOI":"10.1371\/journal.pone.0002492","article-title":"Germline mutation in RNASEL predicts increased risk of head and neck, uterine cervix and breast cancer.","volume":"3","author":"Madsen","year":"2008","journal-title":"PLoS One."},{"key":"B64","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/ng823","article-title":"Germline mutations in the ribonuclease L gene in families showing linkage with HPC1.","volume":"30","author":"Carpten","year":"2002","journal-title":"Nat Genet."},{"key":"B65","doi-asserted-by":"publisher","first-page":"R58","DOI":"10.1186\/bcr3669","article-title":"Rare key functional domain missense substitutions in MRE11A, RAD50, and NBN contribute to breast cancer susceptibility: Results from a Breast Cancer Family Registry case-control mutation-screening study.","volume":"16","author":"Damiola","year":"2014","journal-title":"Breast Cancer Res."},{"key":"B66","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1093\/bioinformatics\/btu703","article-title":"A deep learning approach for annotating the pathogenicity of genetic variants.","volume":"31","author":"Quang","year":"2015","journal-title":"Bioinformatics."},{"key":"B67","doi-asserted-by":"publisher","first-page":"1989","DOI":"10.1002\/cncr.26506","article-title":"MutYH mutation carriers have increased breast cancer risk.","volume":"118","author":"Rennert","year":"2012","journal-title":"Cancer."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.894358\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T06:24:03Z","timestamp":1660199043000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.894358\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,11]]},"references-count":67,"alternative-id":["10.3389\/fmed.2022.894358"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2022.894358","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,11]]},"article-number":"894358"}}