{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T14:03:24Z","timestamp":1784037804467,"version":"3.55.0"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2015,10,5]],"date-time":"2015-10-05T00:00:00Z","timestamp":1444003200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0139753","type":"journal-article","created":{"date-parts":[[2015,10,5]],"date-time":"2015-10-05T14:03:03Z","timestamp":1444053783000},"page":"e0139753","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":33,"title":["Clinical and Molecular Characterization of Brazilian Patients Suspected to Have Lynch Syndrome"],"prefix":"10.1371","volume":"10","author":[{"given":"Felipe","family":"Carneiro da Silva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Roberto de Oliveira","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovana Tardin","family":"Torrezan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1rcia Cristina Pena","family":"Figueiredo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9rika Maria Monteiro","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilson Toshihiko","family":"Nakagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael Canfield","family":"Brianese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ligia","family":"Petrolini de Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Dirlei","family":"Begnani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Aguiar-Junior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedito Mauro","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e1bio de Oliveira","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirce Maria","family":"Carraro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2015,10,5]]},"reference":[{"issue":"4","key":"ref1","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1038\/sj.ejhg.5201584","article-title":"Phenotypic and genotypic heterogeneity in the Lynch syndrome: diagnostic, surveillance and management implications","volume":"14","author":"HT Lynch","year":"2006","journal-title":"Eur J Hum Genet"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1007\/BF02053699","article-title":"The international collaborative group on hereditary non-polyposis colorectal cancer (ICG-HNPCC)","volume":"34","author":"HF Vasen","year":"1991","journal-title":"Dis Colon Rectum"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1016\/S0016-5085(99)70510-X","article-title":"New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC","volume":"116","author":"HF Vasen","year":"1999","journal-title":"Gastroenterology"},{"issue":"23","key":"ref4","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1093\/jnci\/89.23.1758","article-title":"A National Cancer Institute Workshop on Hereditary Nonpolyposis Colorectal Cancer Syndrome: meeting highlights and Bethesda guidelines","volume":"89","author":"MA Rodriguez-Bigas","year":"1997","journal-title":"J Natl Cancer Inst"},{"issue":"4","key":"ref5","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1093\/jnci\/djh034","article-title":"Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability","volume":"96","author":"A Umar","year":"2004","journal-title":"J Natl Cancer Inst"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1016\/0092-8674(93)90331-J","article-title":"Hypermutability and mismatch repair deficiency in RER* tumor cells","volume":"75","author":"R Parsons","year":"1993","journal-title":"Cell"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1038\/368258a0","article-title":"Mutation in the DNA mismatch repair gene homologue hMLHI is associated with hereditary non-polyposis colon cancer","volume":"368","author":"CE Bronner","year":"1994","journal-title":"Nature"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1126\/science.8128251","article-title":"Mutation of a mutL homolog in hereditary colon cancer","volume":"263","author":"N Papadopoulos","year":"1994","journal-title":"Science"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1002\/1098-1004(200012)16:6<530::AID-HUMU15>3.0.CO;2-6","article-title":"Polymorphisms in a pseudogene highly homologous to PMS2","volume":"16","author":"RB Chadwick","year":"2000","journal-title":"Hum Mutat"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1002\/humu.20457","article-title":"Extensive gene conversion at the PMS2 DNA mismatch repair locus","volume":"28","author":"BE Hayward","year":"2007","journal-title":"Hum Mutat"},{"issue":"5","key":"ref11","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1002\/humu.20318","article-title":"Long-range PCR facilitates the identification of PMS2-specific mutations","volume":"27","author":"M Clendenning","year":"2006","journal-title":"Hum Mutat"},{"issue":"4","key":"ref12","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1007\/s10689-011-9461-y","article-title":"Characterization of germline mutations of MLH1 and MSH2 in unrelated south American suspected Lynch syndrome individuals","volume":"10","author":"MD Valentin","year":"2011","journal-title":"Fam Cancer"},{"issue":"4","key":"ref13","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1007\/s10689-012-9550-6","article-title":"Bethesda criteria for microsatellite instability testing: impact on the detection of new cases of Lynch syndrome","volume":"11","author":"M Serrano","year":"2012","journal-title":"Fam Cancer"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1093\/jnci\/djp473","article-title":"Risks of Lynch Syndrome Cancers for MSH6 Mutation Carriers","volume":"102","author":"L Baglietto","year":"2010","journal-title":"J Natl Cancer Inst"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"4486","DOI":"10.1200\/JCO.2004.02.033","article-title":"Lower incidence of colorectal cancer and later age of disease onset in 27 families with pathogenic MSH6 germline mutations com- pared with families with MLH1 or MSH2 mutations: the German Hereditary Nonpolyposis Colorectal Cancer Consortium","volume":"22","author":"J Plaschke","year":"2004","journal-title":"J Clin Oncol"},{"issue":"1","key":"ref16","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1053\/j.gastro.2004.03.068","article-title":"Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations:impact on counseling and surveillance","volume":"127","author":"YM Hendriks","year":"2004","journal-title":"Gastroenterology"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1086\/421332","article-title":"Penetrance and expressivity of MSH6 germline mutations in seven kindreds not ascertained by family history","volume":"74","author":"BM Buttin","year":"2004","journal-title":"Am J Hum Genet"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1136\/jmg.38.5.318","article-title":"Atypical HNPCC owing to MSH6 germline mutations: analysis of a large Dutch pedigree","volume":"38","author":"A Wagner","year":"2001","journal-title":"J Med Genet"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1002\/ijc.11718","article-title":"Mutation analysis of the MLH1, MSH2 and MSH6 genes in patients with double primary cancers of the colorectum and the endometrium: a population-based study in northern Sweden","volume":"109","author":"K Cederquist","year":"2004","journal-title":"Int J Cancer"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s10689-007-9145-9","article-title":"The biochemical basis of microsatellite instability and abnormal immunohistochemistry and clinical behavior in Lynch syndrome: from bench to bedside","volume":"7","author":"CR Boland","year":"2008","journal-title":"Fam Cancer"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1002\/(SICI)1097-0215(19990812)82:4<516::AID-IJC8>3.0.CO;2-U","article-title":"Gene-environment interaction in hereditary nonpolyposis colorectal cancer with implications for diagnosis and genetic testing","volume":"15","author":"J-G Park","year":"1999","journal-title":"Int J Cancer"},{"issue":"1","key":"ref22","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/ng.283","article-title":"Heritable somatic methylation and inactivation of MSH2 in families with Lynchsyndrome due to deletion of the 3&apos; exons of TACSTD1","volume":"41","author":"MJ Ligtenberg","year":"2009","journal-title":"Nat Genet"},{"issue":"2","key":"ref23","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1002\/humu.20942","article-title":"Deletions removing the last exon of TACSTD1 constitute a distinct class of mutations predisposing to Lynch syndrome","volume":"30","author":"ME Kovacs","year":"2009","journal-title":"Hum Mutat"},{"issue":"1","key":"ref24","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/ng.283","article-title":"Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3&apos; exons of TACSTD1","volume":"41","author":"MJ Ligtenberg","year":"2009","journal-title":"Nat Genet"},{"issue":"10","key":"ref25","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1158\/1940-6207.CAPR-11-0080","article-title":"Frequency of rearrangements in Lynch syndrome cases associated with MSH2: characterization of a new deletion involving both EPCAM and the 5&apos; part of MSH2","volume":"4","author":"L P\u00e9rez-Cabornero","year":"2011","journal-title":"Cancer Prev Res (Phila)"},{"issue":"52","key":"ref26","doi-asserted-by":"crossref","first-page":"22223","DOI":"10.1073\/pnas.0912250106","article-title":"A conserved MutS homolog connector domain interface interacts with MutL homologs","volume":"106","author":"ML Mendillo","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"8","key":"ref27","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1002\/humu.21301","article-title":"Identification of Lynch syndrome mutations in the MLH1-PMS2 interface that disturb dimerization and mismatch repair","volume":"31","author":"J Kosinski","year":"2010","journal-title":"Hum Mutat"},{"issue":"9","key":"ref28","doi-asserted-by":"crossref","first-page":"2432","DOI":"10.1158\/1078-0432.CCR-12-3299","article-title":"Expression defect size among unclassified MLH1 variants determines pathogenicity in Lynch syndrome diagnosis","volume":"19","author":"I Hinrichsen","year":"2013","journal-title":"Clin Cancer Res"},{"issue":"9","key":"ref29","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1136\/jmg.37.9.641","article-title":"Sensitivity and specificity of clinical criteria for hereditary non-polyposis colorectal cancer associated mutations in MSH2 and MLH1","volume":"37","author":"S Syngal","year":"2000","journal-title":"J Med Genet"},{"issue":"6","key":"ref30","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1136\/gutjnl-2012-304356","article-title":"Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts","volume":"62","author":"HF Vasen","year":"2013","journal-title":"Gut"},{"issue":"18","key":"ref31","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1093\/jnci\/djs351","article-title":"Risks of primary extracolonic cancers following colorectal cancer in lynch syndrome","volume":"104","author":"AK Win","year":"2012","journal-title":"J Natl Cancer Inst"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1002\/jso.23054","article-title":"Tumor spectrum in lynch syndrome, DNA mismatch repair system and endogenous carcinogens","volume":"106","author":"V Medina-Arana","year":"2012","journal-title":"J Surg Oncol"},{"issue":"3","key":"ref33","doi-asserted-by":"crossref","first-page":"R90","DOI":"10.1186\/bcr3205","article-title":"Breast carcinoma and Lynch syndrome: molecular analysis of tumors arising in mutation carriers, non-carriers, and sporadic cases","volume":"14","author":"JE Lotsari","year":"2012","journal-title":"Breast Cancer Res"},{"issue":"2","key":"ref34","doi-asserted-by":"crossref","first-page":"R27","DOI":"10.1186\/bcr3405","article-title":"Risk of breast cancer in Lynch syndrome: a systematic review","volume":"15","author":"AK Win","year":"2013","journal-title":"Breast Cancer Res"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1155\/2004\/305058","article-title":"Mutations associated with HNPCC predisposition\u2013update of ICG-HNPCC\/INSiGHT mutation database","volume":"20","author":"P Peltomaki","year":"2004","journal-title":"Dis Markers"},{"issue":"6","key":"ref36","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1053\/j.gastro.2014.08.041","article-title":"Colon and endometrial cancers with mismatch repair deficiency can arise from somatic, rather than germline, mutations","volume":"147","author":"S Haraldsdottir","year":"2014","journal-title":"Gastroenterology"},{"issue":"9","key":"ref37","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1002\/cncr.29190","article-title":"Prevalence of somatic mutl homolog 1 promoter hypermethylation in Lynch syndrome colorectal cancer","volume":"121","author":"L Moreira","year":"2015","journal-title":"Cancer"},{"issue":"11","key":"ref38","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1002\/humu.22142","article-title":"Comprehensive functional assessment of MLH1 variants of unknown significance","volume":"33","author":"E Borr\u00e0s","year":"2012","journal-title":"Hum Mutat"},{"issue":"6","key":"ref39","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1111\/cge.12467","article-title":"Detailed characterization of MLH1 p.D41H and p.N710D variants coexisting in a Lynch syndrome family with conserved MLH1 expression tumors","volume":"87","author":"M Pineda","year":"2015","journal-title":"Clin Genet"},{"issue":"10","key":"ref40","doi-asserted-by":"crossref","first-page":"5908","DOI":"10.1073\/pnas.1030231100","article-title":"Prevalence of defective DNA mismatch repair and MSH6 mutation in an unselected series of endometrial cancers","volume":"100","author":"PJ Goodfellow","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"issue":"6","key":"ref41","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1136\/jmedgenet-2014-102284","article-title":"Diagnostic criteria for constitutional mismatch repair deficiency syndrome:suggestions of the European consortium &apos;care for CMMRD&apos; (C4CMMRD)","volume":"51","author":"K Wimmer","year":"2014","journal-title":"J Med Genet"},{"issue":"6","key":"ref42","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1111\/j.1399-0004.2007.00803.x","article-title":"Constitutive deficiency in DNA mismatch repair","volume":"71","author":"KE Felton","year":"2007","journal-title":"Clin Genet"},{"issue":"5","key":"ref43","doi-asserted-by":"crossref","first-page":"841","DOI":"10.3324\/haematol.2009.015503","article-title":"Constitutional mismatch repair deficiency and childhood leukemia\/lymphoma\u2014report on a novel biallelic MSH6 mutation","volume":"95","author":"T Ripperger","year":"2010","journal-title":"Haematologica"},{"issue":"4","key":"ref44","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1200\/JCO.2014.57.8088","article-title":"Lynch Syndrome Caused by Germline PMS2 Mutations: Delineating the Cancer Risk","volume":"33","author":"SW Ten Broeke","year":"2015","journal-title":"J Clin Oncol"},{"issue":"4","key":"ref45","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.soc.2009.07.007","article-title":"Role of MSH6 and PMS2 in the DNA mismatch repair process and carcinogenesis","volume":"18","author":"MA Jenkins","year":"2009","journal-title":"Surg Oncol Clin N Am"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0139753","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,8,31]],"date-time":"2019-08-31T03:16:54Z","timestamp":1567221414000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0139753"}},"subtitle":[],"editor":[{"given":"Hiromu","family":"Suzuki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,10,5]]},"references-count":45,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2015,10,5]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0139753","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10,5]]}}}