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Identification of c.1531C>T Pathogenic Variant in the CDH1 Gene as a Novel Germline Mutation of Hereditary Diffuse Gastric Cancer

Germline pathogenic variants in the CDH1 gene are a well-established cause of hereditary diffuse gastric cancer (HDGC) syndrome. The aim of this study was to characterize CDH1 mutations associated with HDGC from Chile, a country with one of the highest incidence and mortality rates in the world for...

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Autores principales: Norero, Enrique, Alarcon, M. Alejandra, Hakkaart, Christopher, de Mayo, Tomas, Mellado, Cecilia, Garrido, Marcelo, Aguayo, Gloria, Lagos, Marcela, Torres, Javiera, Calvo, Alfonso, Guilford, Parry, Corvalan, Alejandro H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829381/
https://www.ncbi.nlm.nih.gov/pubmed/31600923
http://dx.doi.org/10.3390/ijms20204980
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author Norero, Enrique
Alarcon, M. Alejandra
Hakkaart, Christopher
de Mayo, Tomas
Mellado, Cecilia
Garrido, Marcelo
Aguayo, Gloria
Lagos, Marcela
Torres, Javiera
Calvo, Alfonso
Guilford, Parry
Corvalan, Alejandro H.
author_facet Norero, Enrique
Alarcon, M. Alejandra
Hakkaart, Christopher
de Mayo, Tomas
Mellado, Cecilia
Garrido, Marcelo
Aguayo, Gloria
Lagos, Marcela
Torres, Javiera
Calvo, Alfonso
Guilford, Parry
Corvalan, Alejandro H.
author_sort Norero, Enrique
collection PubMed
description Germline pathogenic variants in the CDH1 gene are a well-established cause of hereditary diffuse gastric cancer (HDGC) syndrome. The aim of this study was to characterize CDH1 mutations associated with HDGC from Chile, a country with one of the highest incidence and mortality rates in the world for gastric cancer (GC). Here, we prospectively include probands with family history/early onset of diffuse-type of GC. The whole coding sequence of the CDH1 gene was sequenced from genomic DNA in all patients, and a multidisciplinary team managed each family member with a pathogenic sequence variant. Thirty-six cases were included (median age 44 years/male 50%). Twenty-seven (75%) patients had diffuse-type GC at ≤50 years of age and 19 (53%) had first or second-degree family members with a history of HDGC. Two cases (5.5%) carried a non-synonymous germline sequence variant in the CDH1 gene: (a) The c.88C>A missense variant was found in a family with three diffuse-type GC cases; and (b) c.1531C>T a nonsense pathogenic variant was identified in a 22-year-old proband with no previous family history of HDGC. Of note, six family members carry the same nonsense pathogenic variant. Prophylactic gastrectomy in the proband’s sister revealed stage I signet-ring cell carcinoma. The finding of 1531C>T pathogenic variant in the CDH1 in proband with no previous family history of HDGC warrants further study to uncover familial clustering of disease in CDH1 negative patients. This finding may be particularly relevant in high incidence countries, such as the case in this report.
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spelling pubmed-68293812019-11-18 Identification of c.1531C>T Pathogenic Variant in the CDH1 Gene as a Novel Germline Mutation of Hereditary Diffuse Gastric Cancer Norero, Enrique Alarcon, M. Alejandra Hakkaart, Christopher de Mayo, Tomas Mellado, Cecilia Garrido, Marcelo Aguayo, Gloria Lagos, Marcela Torres, Javiera Calvo, Alfonso Guilford, Parry Corvalan, Alejandro H. Int J Mol Sci Article Germline pathogenic variants in the CDH1 gene are a well-established cause of hereditary diffuse gastric cancer (HDGC) syndrome. The aim of this study was to characterize CDH1 mutations associated with HDGC from Chile, a country with one of the highest incidence and mortality rates in the world for gastric cancer (GC). Here, we prospectively include probands with family history/early onset of diffuse-type of GC. The whole coding sequence of the CDH1 gene was sequenced from genomic DNA in all patients, and a multidisciplinary team managed each family member with a pathogenic sequence variant. Thirty-six cases were included (median age 44 years/male 50%). Twenty-seven (75%) patients had diffuse-type GC at ≤50 years of age and 19 (53%) had first or second-degree family members with a history of HDGC. Two cases (5.5%) carried a non-synonymous germline sequence variant in the CDH1 gene: (a) The c.88C>A missense variant was found in a family with three diffuse-type GC cases; and (b) c.1531C>T a nonsense pathogenic variant was identified in a 22-year-old proband with no previous family history of HDGC. Of note, six family members carry the same nonsense pathogenic variant. Prophylactic gastrectomy in the proband’s sister revealed stage I signet-ring cell carcinoma. The finding of 1531C>T pathogenic variant in the CDH1 in proband with no previous family history of HDGC warrants further study to uncover familial clustering of disease in CDH1 negative patients. This finding may be particularly relevant in high incidence countries, such as the case in this report. MDPI 2019-10-09 /pmc/articles/PMC6829381/ /pubmed/31600923 http://dx.doi.org/10.3390/ijms20204980 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Norero, Enrique
Alarcon, M. Alejandra
Hakkaart, Christopher
de Mayo, Tomas
Mellado, Cecilia
Garrido, Marcelo
Aguayo, Gloria
Lagos, Marcela
Torres, Javiera
Calvo, Alfonso
Guilford, Parry
Corvalan, Alejandro H.
Identification of c.1531C>T Pathogenic Variant in the CDH1 Gene as a Novel Germline Mutation of Hereditary Diffuse Gastric Cancer
title Identification of c.1531C>T Pathogenic Variant in the CDH1 Gene as a Novel Germline Mutation of Hereditary Diffuse Gastric Cancer
title_full Identification of c.1531C>T Pathogenic Variant in the CDH1 Gene as a Novel Germline Mutation of Hereditary Diffuse Gastric Cancer
title_fullStr Identification of c.1531C>T Pathogenic Variant in the CDH1 Gene as a Novel Germline Mutation of Hereditary Diffuse Gastric Cancer
title_full_unstemmed Identification of c.1531C>T Pathogenic Variant in the CDH1 Gene as a Novel Germline Mutation of Hereditary Diffuse Gastric Cancer
title_short Identification of c.1531C>T Pathogenic Variant in the CDH1 Gene as a Novel Germline Mutation of Hereditary Diffuse Gastric Cancer
title_sort identification of c.1531c>t pathogenic variant in the cdh1 gene as a novel germline mutation of hereditary diffuse gastric cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829381/
https://www.ncbi.nlm.nih.gov/pubmed/31600923
http://dx.doi.org/10.3390/ijms20204980
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