Cargando…
A Hereditable Mutation of MSH2 Gene Associated with Lynch Syndrome in a Five Generation Chinese Family
PURPOSE: In order to clarify which variants of the MMR gene could provide current “healthy” members in affected families a more accurate risk assessment or predictive testing. PATIENTS AND METHODS: One family, which meets the criteria according to both Amsterdam I/II and Bethesda guidelines, is repo...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7051253/ https://www.ncbi.nlm.nih.gov/pubmed/32161499 http://dx.doi.org/10.2147/CMAR.S222572 |
_version_ | 1783502735595798528 |
---|---|
author | Shao, Wei-Hua Wang, Cheng-Yu Wang, Lei-Yun Xiao, Fan Xiao, De-Sheng Yang, Hao Long, Xue-Ying Zhang, Le Luo, Heng-Gui Yin, Ji-Ye Wu, Wei |
author_facet | Shao, Wei-Hua Wang, Cheng-Yu Wang, Lei-Yun Xiao, Fan Xiao, De-Sheng Yang, Hao Long, Xue-Ying Zhang, Le Luo, Heng-Gui Yin, Ji-Ye Wu, Wei |
author_sort | Shao, Wei-Hua |
collection | PubMed |
description | PURPOSE: In order to clarify which variants of the MMR gene could provide current “healthy” members in affected families a more accurate risk assessment or predictive testing. PATIENTS AND METHODS: One family, which meets the criteria according to both Amsterdam I/II and Bethesda guidelines, is reported in this study. The proband and some relatives of the patient have been investigated for whole genome sequencing, microsatellite instability, immunohistochemical MMR protein staining and verified by Sanger sequencing. RESULTS: A heterozygous insertion of uncertain significance (c.420dup, p.Met141Tyrfs) in MSH2 gene was found in proband (III-16) and part of His relatives. The variant was associated with a lack of expression of MSH2 protein (MMR deficient) and high microsatellite instability analysis (MSI) status in tumor tissues of LS patients. In addition, we found that the variant could affect the expression of MSH2 and the response to chemotherapy drugs in vitro. CONCLUSION: We identified an insertion mutation (rs1114167810, c.420dup, p.Met141Tyrfs) in MSH2 in LS using whole genome-wide sequencing (WGS). We further confirmed that this mutation plays an important role in LS patients of this pedigree based on in vivo and vitro study. |
format | Online Article Text |
id | pubmed-7051253 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-70512532020-03-11 A Hereditable Mutation of MSH2 Gene Associated with Lynch Syndrome in a Five Generation Chinese Family Shao, Wei-Hua Wang, Cheng-Yu Wang, Lei-Yun Xiao, Fan Xiao, De-Sheng Yang, Hao Long, Xue-Ying Zhang, Le Luo, Heng-Gui Yin, Ji-Ye Wu, Wei Cancer Manag Res Original Research PURPOSE: In order to clarify which variants of the MMR gene could provide current “healthy” members in affected families a more accurate risk assessment or predictive testing. PATIENTS AND METHODS: One family, which meets the criteria according to both Amsterdam I/II and Bethesda guidelines, is reported in this study. The proband and some relatives of the patient have been investigated for whole genome sequencing, microsatellite instability, immunohistochemical MMR protein staining and verified by Sanger sequencing. RESULTS: A heterozygous insertion of uncertain significance (c.420dup, p.Met141Tyrfs) in MSH2 gene was found in proband (III-16) and part of His relatives. The variant was associated with a lack of expression of MSH2 protein (MMR deficient) and high microsatellite instability analysis (MSI) status in tumor tissues of LS patients. In addition, we found that the variant could affect the expression of MSH2 and the response to chemotherapy drugs in vitro. CONCLUSION: We identified an insertion mutation (rs1114167810, c.420dup, p.Met141Tyrfs) in MSH2 in LS using whole genome-wide sequencing (WGS). We further confirmed that this mutation plays an important role in LS patients of this pedigree based on in vivo and vitro study. Dove 2020-02-27 /pmc/articles/PMC7051253/ /pubmed/32161499 http://dx.doi.org/10.2147/CMAR.S222572 Text en © 2020 Shao et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Shao, Wei-Hua Wang, Cheng-Yu Wang, Lei-Yun Xiao, Fan Xiao, De-Sheng Yang, Hao Long, Xue-Ying Zhang, Le Luo, Heng-Gui Yin, Ji-Ye Wu, Wei A Hereditable Mutation of MSH2 Gene Associated with Lynch Syndrome in a Five Generation Chinese Family |
title | A Hereditable Mutation of MSH2 Gene Associated with Lynch Syndrome in a Five Generation Chinese Family |
title_full | A Hereditable Mutation of MSH2 Gene Associated with Lynch Syndrome in a Five Generation Chinese Family |
title_fullStr | A Hereditable Mutation of MSH2 Gene Associated with Lynch Syndrome in a Five Generation Chinese Family |
title_full_unstemmed | A Hereditable Mutation of MSH2 Gene Associated with Lynch Syndrome in a Five Generation Chinese Family |
title_short | A Hereditable Mutation of MSH2 Gene Associated with Lynch Syndrome in a Five Generation Chinese Family |
title_sort | hereditable mutation of msh2 gene associated with lynch syndrome in a five generation chinese family |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7051253/ https://www.ncbi.nlm.nih.gov/pubmed/32161499 http://dx.doi.org/10.2147/CMAR.S222572 |
work_keys_str_mv | AT shaoweihua ahereditablemutationofmsh2geneassociatedwithlynchsyndromeinafivegenerationchinesefamily AT wangchengyu ahereditablemutationofmsh2geneassociatedwithlynchsyndromeinafivegenerationchinesefamily AT wangleiyun ahereditablemutationofmsh2geneassociatedwithlynchsyndromeinafivegenerationchinesefamily AT xiaofan ahereditablemutationofmsh2geneassociatedwithlynchsyndromeinafivegenerationchinesefamily AT xiaodesheng ahereditablemutationofmsh2geneassociatedwithlynchsyndromeinafivegenerationchinesefamily AT yanghao ahereditablemutationofmsh2geneassociatedwithlynchsyndromeinafivegenerationchinesefamily AT longxueying ahereditablemutationofmsh2geneassociatedwithlynchsyndromeinafivegenerationchinesefamily AT zhangle ahereditablemutationofmsh2geneassociatedwithlynchsyndromeinafivegenerationchinesefamily AT luohenggui ahereditablemutationofmsh2geneassociatedwithlynchsyndromeinafivegenerationchinesefamily AT yinjiye ahereditablemutationofmsh2geneassociatedwithlynchsyndromeinafivegenerationchinesefamily AT wuwei ahereditablemutationofmsh2geneassociatedwithlynchsyndromeinafivegenerationchinesefamily AT shaoweihua hereditablemutationofmsh2geneassociatedwithlynchsyndromeinafivegenerationchinesefamily AT wangchengyu hereditablemutationofmsh2geneassociatedwithlynchsyndromeinafivegenerationchinesefamily AT wangleiyun hereditablemutationofmsh2geneassociatedwithlynchsyndromeinafivegenerationchinesefamily AT xiaofan hereditablemutationofmsh2geneassociatedwithlynchsyndromeinafivegenerationchinesefamily AT xiaodesheng hereditablemutationofmsh2geneassociatedwithlynchsyndromeinafivegenerationchinesefamily AT yanghao hereditablemutationofmsh2geneassociatedwithlynchsyndromeinafivegenerationchinesefamily AT longxueying hereditablemutationofmsh2geneassociatedwithlynchsyndromeinafivegenerationchinesefamily AT zhangle hereditablemutationofmsh2geneassociatedwithlynchsyndromeinafivegenerationchinesefamily AT luohenggui hereditablemutationofmsh2geneassociatedwithlynchsyndromeinafivegenerationchinesefamily AT yinjiye hereditablemutationofmsh2geneassociatedwithlynchsyndromeinafivegenerationchinesefamily AT wuwei hereditablemutationofmsh2geneassociatedwithlynchsyndromeinafivegenerationchinesefamily |