Phenotypic Heterogeneity by Germline Mismatch Repair Gene Defect in Lynch Syndrome Patients
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/7774 |
Resumo: | Introduction: Lynch syndrome is the most common form of hereditary colorectal cancer, being also responsible for endometrial and other types of cancers. It is associated with germline mutations in DNA mismatch repair genes and microsatellite instability. MLH1 and MSH2 mutations have a “classical” Lynch syndrome phenotype, with MSH2 having a higher association with extracolonic cancer. MSH6 and PMS2 mutations have an atypical phenotype. Clinical expression is heterogeneous, with correlation between mismatch repair mutated gene and phenotypic patterns.Material and Methods: We retrospectively analyzed data from patients fulfilling Amsterdam criteria or having mismatch repair gene mutations, between September 2012 and October 2015.Results: We identified 28 patients. Seventeen had colorectal cancer with right colon predominance. Five developed endometrial cancer (median age of diagnosis – 53), with no MSH6 mutations. Five developed other cancers. All mutated mismatch repair cases studied had microsatellite instability.Discussion: Most cases had MSH2 mutations despite MLH1 being described in the literature as the most frequently mutated. Interestingly, colorectal cancer patients showed no tendency for high inflammatory infiltrate. Despite the high incidence of synchronous and metachronous tumours, most patients underwent a partial colectomy. Prophylactic hysterectomy and adnexectomy was performed in menopausal/perimenopausal patients.Conclusion: A standardized registration of patient’s data may lead to better management and knowledge about Lynch syndrome. Use of Bethesda Guidelines might identify new cases non-identified by Amsterdam criteria. Microsatellite instability analysis must be performed in a much larger scale. The genotypic/phenotypic correlation described in the literature was not verified in our study with statistical significance, perhaps due to small data sample and insufficient clinical registration. |
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Phenotypic Heterogeneity by Germline Mismatch Repair Gene Defect in Lynch Syndrome PatientsHeterogeneidade Fenotípica por Mutação Germinativa nos Genes Mismatch Repair em Doentes com Síndrome de LynchColorectal NeoplasmsHereditary NonpolyposisDNA Mismatch RepairDNA Repair-Deficiency DisordersEndometrial NeoplasmsNeoplastic SyndromesHereditary.Neoplasias Colorretais Hereditárias sem PoliposeNeoplasias do EndométrioReparação de Incompatibilidade de ADNSíndromes Neoplásicas HereditáriasTranstornos por Deficiências na Reparação de ADN.Introduction: Lynch syndrome is the most common form of hereditary colorectal cancer, being also responsible for endometrial and other types of cancers. It is associated with germline mutations in DNA mismatch repair genes and microsatellite instability. MLH1 and MSH2 mutations have a “classical” Lynch syndrome phenotype, with MSH2 having a higher association with extracolonic cancer. MSH6 and PMS2 mutations have an atypical phenotype. Clinical expression is heterogeneous, with correlation between mismatch repair mutated gene and phenotypic patterns.Material and Methods: We retrospectively analyzed data from patients fulfilling Amsterdam criteria or having mismatch repair gene mutations, between September 2012 and October 2015.Results: We identified 28 patients. Seventeen had colorectal cancer with right colon predominance. Five developed endometrial cancer (median age of diagnosis – 53), with no MSH6 mutations. Five developed other cancers. All mutated mismatch repair cases studied had microsatellite instability.Discussion: Most cases had MSH2 mutations despite MLH1 being described in the literature as the most frequently mutated. Interestingly, colorectal cancer patients showed no tendency for high inflammatory infiltrate. Despite the high incidence of synchronous and metachronous tumours, most patients underwent a partial colectomy. Prophylactic hysterectomy and adnexectomy was performed in menopausal/perimenopausal patients.Conclusion: A standardized registration of patient’s data may lead to better management and knowledge about Lynch syndrome. Use of Bethesda Guidelines might identify new cases non-identified by Amsterdam criteria. Microsatellite instability analysis must be performed in a much larger scale. The genotypic/phenotypic correlation described in the literature was not verified in our study with statistical significance, perhaps due to small data sample and insufficient clinical registration.Introdução: A síndrome de Lynch é a forma hereditária mais comum de cancro colo-rectal, sendo também responsável por cancro do endométrio e de outros tipos. Associa-se a mutações germinativas nos genes de mismatch repair do ADN e a instabilidade de microssatélites. As mutações MLH1 e MSH2 têm um fenótipo de síndrome de Lynch ‘clássico’, sendo o MSH2 mais associado a cancro extra-cólico. Mutações do MSH6 e PMS2 têm um fenótipo atípico. A expressão clínica é heterogénea, existindo uma correlação entre o gene mismatch repair mutado e o padrão fenotípico.Material e Métodos: Análise retrospetiva dos dados clínicos de doentes que cumpriam os critérios de Amesterdão ou que tinha mutações nos genes mismatch repair, entre setembro de 2012 e outubro de 2015.Resultados: Identificámos 28 doentes. Dezassete tinham cancro colo-rectal sendo a localização no cólon direito predominante. Cinco tiveram cancro do endométrio (mediana da idade de diagnóstico – 53), sem qualquer mutação no MSH6. Cinco desenvolveram outros cancros. Todos os casos com mutações mismatch repair estudados tinham instabilidade de microssatélites.Discussão: Na maioria dos casos foi encontrada mutação no MSH2 apesar de o MLH1 ser descrito na literatura como o gene mais frequentemente mutado. Interessa dizer que os doentes com cancro colo-rectal não evidenciam uma tendência para ter muito infiltrado inflamatório. Na maioria dos casos foi realizada colectomia parcial apesar da incidência elevada de lesões síncronas e metácronas associadas. Histerectomia e anexectomia profilática foi realizada em doentes em menopausa/perimenopausa.Conclusão: O registo standardizado dos dados dos doentes poderá levar a um melhor acompanhamento e conhecimento desta síndrome. O uso das Guidelines de Bethesda poderá identificar novos casos que escapam aos critérios de Amesterdão. A pesquisa de instabilidade de microssatélites deve ser feita em muito maior número. Embora seja descrita na literatura uma correlação genótipo/fenótipo, o nosso estudo não verificou esta correlação de forma estatisticamente signficativa, talvez por a amostra ser pequena e os registos clínicos insuficientes.Ordem dos Médicos2016-10-31info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttps://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/7774oai:ojs.www.actamedicaportuguesa.com:article/7774Acta Médica Portuguesa; Vol. 29 No. 10 (2016): October; 587-596Acta Médica Portuguesa; Vol. 29 N.º 10 (2016): Outubro; 587-5961646-07580870-399Xreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAPenghttps://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/7774https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/7774/4781https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/7774/8443https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/7774/8490https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/7774/8625Direitos de Autor (c) 2016 Acta Médica Portuguesainfo:eu-repo/semantics/openAccessHernâni-Eusébio, JorgeBarbosa, Elisabete2022-12-20T11:05:19Zoai:ojs.www.actamedicaportuguesa.com:article/7774Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T16:19:29.950591Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Phenotypic Heterogeneity by Germline Mismatch Repair Gene Defect in Lynch Syndrome Patients Heterogeneidade Fenotípica por Mutação Germinativa nos Genes Mismatch Repair em Doentes com Síndrome de Lynch |
title |
Phenotypic Heterogeneity by Germline Mismatch Repair Gene Defect in Lynch Syndrome Patients |
spellingShingle |
Phenotypic Heterogeneity by Germline Mismatch Repair Gene Defect in Lynch Syndrome Patients Hernâni-Eusébio, Jorge Colorectal Neoplasms Hereditary Nonpolyposis DNA Mismatch Repair DNA Repair-Deficiency Disorders Endometrial Neoplasms Neoplastic Syndromes Hereditary. Neoplasias Colorretais Hereditárias sem Polipose Neoplasias do Endométrio Reparação de Incompatibilidade de ADN Síndromes Neoplásicas Hereditárias Transtornos por Deficiências na Reparação de ADN. |
title_short |
Phenotypic Heterogeneity by Germline Mismatch Repair Gene Defect in Lynch Syndrome Patients |
title_full |
Phenotypic Heterogeneity by Germline Mismatch Repair Gene Defect in Lynch Syndrome Patients |
title_fullStr |
Phenotypic Heterogeneity by Germline Mismatch Repair Gene Defect in Lynch Syndrome Patients |
title_full_unstemmed |
Phenotypic Heterogeneity by Germline Mismatch Repair Gene Defect in Lynch Syndrome Patients |
title_sort |
Phenotypic Heterogeneity by Germline Mismatch Repair Gene Defect in Lynch Syndrome Patients |
author |
Hernâni-Eusébio, Jorge |
author_facet |
Hernâni-Eusébio, Jorge Barbosa, Elisabete |
author_role |
author |
author2 |
Barbosa, Elisabete |
author2_role |
author |
dc.contributor.author.fl_str_mv |
Hernâni-Eusébio, Jorge Barbosa, Elisabete |
dc.subject.por.fl_str_mv |
Colorectal Neoplasms Hereditary Nonpolyposis DNA Mismatch Repair DNA Repair-Deficiency Disorders Endometrial Neoplasms Neoplastic Syndromes Hereditary. Neoplasias Colorretais Hereditárias sem Polipose Neoplasias do Endométrio Reparação de Incompatibilidade de ADN Síndromes Neoplásicas Hereditárias Transtornos por Deficiências na Reparação de ADN. |
topic |
Colorectal Neoplasms Hereditary Nonpolyposis DNA Mismatch Repair DNA Repair-Deficiency Disorders Endometrial Neoplasms Neoplastic Syndromes Hereditary. Neoplasias Colorretais Hereditárias sem Polipose Neoplasias do Endométrio Reparação de Incompatibilidade de ADN Síndromes Neoplásicas Hereditárias Transtornos por Deficiências na Reparação de ADN. |
description |
Introduction: Lynch syndrome is the most common form of hereditary colorectal cancer, being also responsible for endometrial and other types of cancers. It is associated with germline mutations in DNA mismatch repair genes and microsatellite instability. MLH1 and MSH2 mutations have a “classical” Lynch syndrome phenotype, with MSH2 having a higher association with extracolonic cancer. MSH6 and PMS2 mutations have an atypical phenotype. Clinical expression is heterogeneous, with correlation between mismatch repair mutated gene and phenotypic patterns.Material and Methods: We retrospectively analyzed data from patients fulfilling Amsterdam criteria or having mismatch repair gene mutations, between September 2012 and October 2015.Results: We identified 28 patients. Seventeen had colorectal cancer with right colon predominance. Five developed endometrial cancer (median age of diagnosis – 53), with no MSH6 mutations. Five developed other cancers. All mutated mismatch repair cases studied had microsatellite instability.Discussion: Most cases had MSH2 mutations despite MLH1 being described in the literature as the most frequently mutated. Interestingly, colorectal cancer patients showed no tendency for high inflammatory infiltrate. Despite the high incidence of synchronous and metachronous tumours, most patients underwent a partial colectomy. Prophylactic hysterectomy and adnexectomy was performed in menopausal/perimenopausal patients.Conclusion: A standardized registration of patient’s data may lead to better management and knowledge about Lynch syndrome. Use of Bethesda Guidelines might identify new cases non-identified by Amsterdam criteria. Microsatellite instability analysis must be performed in a much larger scale. The genotypic/phenotypic correlation described in the literature was not verified in our study with statistical significance, perhaps due to small data sample and insufficient clinical registration. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-10-31 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/7774 oai:ojs.www.actamedicaportuguesa.com:article/7774 |
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https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/7774 |
identifier_str_mv |
oai:ojs.www.actamedicaportuguesa.com:article/7774 |
dc.language.iso.fl_str_mv |
eng |
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eng |
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https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/7774 https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/7774/4781 https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/7774/8443 https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/7774/8490 https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/7774/8625 |
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Direitos de Autor (c) 2016 Acta Médica Portuguesa info:eu-repo/semantics/openAccess |
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Direitos de Autor (c) 2016 Acta Médica Portuguesa |
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openAccess |
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application/pdf application/pdf application/pdf application/pdf |
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Ordem dos Médicos |
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Ordem dos Médicos |
dc.source.none.fl_str_mv |
Acta Médica Portuguesa; Vol. 29 No. 10 (2016): October; 587-596 Acta Médica Portuguesa; Vol. 29 N.º 10 (2016): Outubro; 587-596 1646-0758 0870-399X reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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