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

Detalhes bibliográficos
Autor(a) principal: Schneider, Nayê Balzan
Data de Publicação: 2018
Outros Autores: Pastor, Tatiane, Paula, André Escremim de, Achatz, Maria Isabel, Santos, Ândrea Ribeiro dos, Vianna, Fernanda Sales Luiz, Rosset, Clévia, Pinheiro, Manuela, Ashton-Prolla, Patricia, Moreira, Miguel Ângelo Martins, Palmero, Edenir Inêz, Vargas, Fernando Regla, Múltipla autoria - ver em Notas
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/30518
Resumo: Brazilian 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).
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spelling Schneider, Nayê BalzanPastor, TatianePaula, André Escremim deAchatz, Maria IsabelSantos, Ândrea Ribeiro dosVianna, Fernanda Sales LuizRosset, CléviaPinheiro, ManuelaAshton-Prolla, PatriciaMoreira, Miguel Ângelo MartinsPalmero, Edenir InêzVargas, Fernando ReglaMúltipla autoria - ver em Notas2018-12-11T16:20:08Z2018-12-11T16:20:08Z2018SCHNEIDER, 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, 2018.2045-7634https://www.arca.fiocruz.br/handle/icict/3051810.1002/cam4.1316Brazilian 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).Hospital de Clínicas de Porto Alegre. Centro de Pesquisa Experimental. Laboratório de Medicina Genômica. Porto Alegre, RS, Brasil / Universidade Federal do Rio Grande do Sul (UFRGS). Programa de Pós-Graduação em Medicina: Ciências Médicas. Porto Alegre, RS, Brasil / Universidade Federal do Rio Grande do Sul. Programa de Pós-Graduação em Genética e Biologia Molecular. Porto Alegre, RS, Brasil.Instituto Nacional de Câncer. Programa de Genética. Rio de Janeiro, RJ, Brasil.Hospital de Câncer de Barretos. Centro de Pesquisa em Oncologia Molecular. Barretos, SP, Brasil.AC Camargo Cancer Center. São Paulo, SP, Brasil. National Institutes of Health. National Cancerr Institute. Department of Health and Human Services. Division of Cancer Epidemiology and Genetics. Clinical Genetics Branch. Bethesda, Maryland, USA.Universidade Federal do Pará. Laboratório de Genética Humana e Médica. Núcleo de Pesquisa em Biociência e Ética na Ciência. Belém, PA, Brasil.Hospital de Clínicas de Porto Alegre. Centro de Pesquisa Experimental. Laboratório de Pesquisa em Bioética e Ética na Ciência. Porto Alegre., RS, Brasil.,Hospital de Clínicas de Porto Alegre. Centro de Pesquisa Experimental. Laboratório de Medicina Genômica. Porto Alegre, RS, Brasil / Universidade Federal do Rio Grande do Sul (UFRGS). Programa de Pós-Graduação em Medicina: Ciências Médicas. Porto Alegre, RS, Brasil / Universidade Federal do Rio Grande do Sul. Programa de Pós-Graduação em Genética e Biologia Molecular. Porto Alegre, RS, Brasil.Instituto Português de Oncologia do Porto. Serviço de Genética. Porto, Portugal.Hospital de Clínicas de Porto Alegre. Centro de Pesquisa Experimental. Laboratório de Medicina Genômica. Porto Alegre, RS, Brasil / Universidade Federal do Rio Grande do Sul (UFRGS). Programa de Pós-Graduação em Medicina: Ciências Médicas. Porto Alegre, RS, Brasil / Universidade Federal do Rio Grande do Sul. Programa de Pós-Graduação em Genética e Biologia Molecular. Porto Alegre, RS, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ. Brasil.Múltiplas afiliações - ver em NotasLynch 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.engWiley Open AccessNeoplasias ColorretaisSíndrome de LinchColorectal cancerLynch syndromeMMR genesNeoplasias ColorretaisNeoplasias Colorretais Hereditárias sem PoliposeReparo de Erro de Pareamento de DNAGermline MLH1, MSH2 and MSH6 variants in Brazilian patients with colorectal cancer and clinical features suggestive of Lynch Syndromeinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; 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dc.title.pt_BR.fl_str_mv Germline MLH1, MSH2 and MSH6 variants in Brazilian patients with colorectal cancer and clinical features suggestive of Lynch Syndrome
title Germline MLH1, MSH2 and MSH6 variants in Brazilian patients with colorectal cancer and clinical features suggestive of Lynch Syndrome
spellingShingle Germline MLH1, MSH2 and MSH6 variants in Brazilian patients with colorectal cancer and clinical features suggestive of Lynch Syndrome
Schneider, Nayê Balzan
Neoplasias Colorretais
Síndrome de Linch
Colorectal cancer
Lynch syndrome
MMR genes
Neoplasias Colorretais
Neoplasias Colorretais Hereditárias sem Polipose
Reparo de Erro de Pareamento de DNA
title_short Germline MLH1, MSH2 and MSH6 variants in Brazilian patients with colorectal cancer and clinical features suggestive of Lynch Syndrome
title_full Germline MLH1, MSH2 and MSH6 variants in Brazilian patients with colorectal cancer and clinical features suggestive of Lynch Syndrome
title_fullStr Germline MLH1, MSH2 and MSH6 variants in Brazilian patients with colorectal cancer and clinical features suggestive of Lynch Syndrome
title_full_unstemmed Germline MLH1, MSH2 and MSH6 variants in Brazilian patients with colorectal cancer and clinical features suggestive of Lynch Syndrome
title_sort Germline MLH1, MSH2 and MSH6 variants in Brazilian patients with colorectal cancer and clinical features suggestive of Lynch Syndrome
author Schneider, Nayê Balzan
author_facet Schneider, Nayê Balzan
Pastor, Tatiane
Paula, André Escremim de
Achatz, Maria Isabel
Santos, Ândrea Ribeiro dos
Vianna, Fernanda Sales Luiz
Rosset, Clévia
Pinheiro, Manuela
Ashton-Prolla, Patricia
Moreira, Miguel Ângelo Martins
Palmero, Edenir Inêz
Vargas, Fernando Regla
Múltipla autoria - ver em Notas
author_role author
author2 Pastor, Tatiane
Paula, André Escremim de
Achatz, Maria Isabel
Santos, Ândrea Ribeiro dos
Vianna, Fernanda Sales Luiz
Rosset, Clévia
Pinheiro, Manuela
Ashton-Prolla, Patricia
Moreira, Miguel Ângelo Martins
Palmero, Edenir Inêz
Vargas, Fernando Regla
Múltipla autoria - ver em Notas
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Schneider, Nayê Balzan
Pastor, Tatiane
Paula, André Escremim de
Achatz, Maria Isabel
Santos, Ândrea Ribeiro dos
Vianna, Fernanda Sales Luiz
Rosset, Clévia
Pinheiro, Manuela
Ashton-Prolla, Patricia
Moreira, Miguel Ângelo Martins
Palmero, Edenir Inêz
Vargas, Fernando Regla
Múltipla autoria - ver em Notas
dc.subject.other.pt_BR.fl_str_mv Neoplasias Colorretais
Síndrome de Linch
topic Neoplasias Colorretais
Síndrome de Linch
Colorectal cancer
Lynch syndrome
MMR genes
Neoplasias Colorretais
Neoplasias Colorretais Hereditárias sem Polipose
Reparo de Erro de Pareamento de DNA
dc.subject.en.pt_BR.fl_str_mv Colorectal cancer
Lynch syndrome
MMR genes
Neoplasias Colorretais
dc.subject.decs.pt_BR.fl_str_mv Neoplasias Colorretais Hereditárias sem Polipose
Reparo de Erro de Pareamento de DNA
description Brazilian 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).
publishDate 2018
dc.date.accessioned.fl_str_mv 2018-12-11T16:20:08Z
dc.date.available.fl_str_mv 2018-12-11T16:20:08Z
dc.date.issued.fl_str_mv 2018
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.citation.fl_str_mv SCHNEIDER, 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.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/30518
dc.identifier.issn.pt_BR.fl_str_mv 2045-7634
dc.identifier.doi.none.fl_str_mv 10.1002/cam4.1316
identifier_str_mv SCHNEIDER, 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.
2045-7634
10.1002/cam4.1316
url https://www.arca.fiocruz.br/handle/icict/30518
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Wiley Open Access
publisher.none.fl_str_mv Wiley Open Access
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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