Germline MLH1, MSH2 and MSH6 variants in Brazilian patients with colorectal cancer and clinical features suggestive of Lynch Syndrome

dc.creatorSchneider, Nayê Balzan
dc.creatorPastor, Tatiane
dc.creatorPaula, André Escremim de
dc.creatorAchatz, Maria Isabel
dc.creatorSantos, Ândrea Ribeiro dos
dc.creatorVianna, Fernanda Sales Luiz
dc.creatorRosset, Clévia
dc.creatorPinheiro, Manuela
dc.creatorAshton-Prolla, Patricia
dc.creatorMoreira, Miguel Ângelo Martins
dc.creatorPalmero, Edenir Inêz
dc.creatorVargas, Fernando Regla
dc.creatorMúltipla autoria - ver em Notas
dc.date2018-12-11T16:20:08Z
dc.date2018-12-11T16:20:08Z
dc.date2018
dc.date.accessioned2023-09-26T20:17:34Z
dc.date.available2023-09-26T20:17:34Z
dc.identifierSCHNEIDER, Nayê Balzan; et al. Germline MLH1, MSH2 and MSH6 variants in Brazilian patients with colorectal cancer and clinical features suggestive of Lynch Syndrome. Cancer Medicine, v.7, n.5, p.2078-2088, 2018.
dc.identifier2045-7634
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/30518
dc.identifier10.1002/cam4.1316
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8853493
dc.descriptionBrazilian Lynch Study Group Patrícia Santos Silva, Patrícia Koehler-Santos, Silvia Liliana Cossio, Cristina Netto, Gustavo Stumpf da Silva (Laboratório de Medicina Genômica, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre (HCPA) and Programa de Pós Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil); Fernando Regla Vargas, Maria Angélica de Lima (Genetics Program Instituto Nacional de Câncer, Rio de Janeiro, Brazil); Cristovam Scapulatempo-Neto, Rui Manuel Reis, André Lopes Carvalho (Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil); Carla Pinto, Manuel Rui Teixeira (Serviço de Genética, Instituto Português de Oncologia do Porto (IPO Porto), Porto, Portugal); Danilo Vilela Viana, Benedito Mauro Rossi Junea Caris Oliveira, Henrique Campos Galvão (Oncogenetics Department, Barretos Cancer Hospital, Barretos, Brazil). Paulo Assumpção, Geraldo Ishak, Sérgio Lima Júnior (Núcleo de Pesquisas Oncológicas, Universidade Federal do Pará e Serviço de Cirurgia Geral e do Aparelho Digestivo, Hospital Universitário João Barros Barreto, Universidade Federal do Pará).
dc.descriptionLynch syndrome (LS) is the most common hereditary colorectal cancer syndrome, caused by germline mutations in one of the major genes involved in mismatch repair (MMR): MLH1, MSH2, MSH6 and more rarely, PMS2. Recently, germline deletions in EPCAM have been also associated to the syndrome. Most of the pathogenic MMR mutations found in LS families occur in MLH1 or MSH2. Gene variants include missense, nonsense, frameshift mutations, large genomic rearrangements and splice-site variants and most of the studies reporting the molecular characterization of LS families have been conducted outside South America. In this study, we analyzed 60 unrelated probands diagnosed with colorectal cancer and LS criteria. Testing for germline mutations and/or rearrangements in the most commonly affected MMR genes (MLH1, MSH2, EPCAM and MSH6) was done by Sanger sequencing and MLPA. Pathogenic or likely pathogenic variants were identified in MLH1 or MSH2 in 21 probands (35.0%). Of these, approximately one-third were gene rearrangements. In addition, nine variants of uncertain significance (VUS) were identified in 10 (16.6%) of the sixty probands analyzed. Other four novel variants were identified, only in MLH1. Our results suggest that MSH6 pathogenic variants are not common among Brazilian LS probands diagnosed with CRC and that MMR gene rearrangements account for a significant proportion of the germline variants in this population underscoring the need to include rearrangement analysis in the molecular testing of Brazilian individuals with suspected Lynch syndrome.
dc.formatapplication/pdf
dc.languageeng
dc.publisherWiley Open Access
dc.rightsopen access
dc.subjectNeoplasias Colorretais
dc.subjectSíndrome de Linch
dc.subjectColorectal cancer
dc.subjectLynch syndrome
dc.subjectMMR genes
dc.subjectNeoplasias Colorretais
dc.subjectNeoplasias Colorretais Hereditárias sem Polipose
dc.subjectReparo de Erro de Pareamento de DNA
dc.titleGermline MLH1, MSH2 and MSH6 variants in Brazilian patients with colorectal cancer and clinical features suggestive of Lynch Syndrome
dc.typeArticle


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