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The role of MYH and microsatellite instability in the development of sporadic colorectal cancer

Biallelic germline mutations in MYH are associated with colorectal neoplasms, which develop through a pathway involving somatic inactivation of APC. In this study, we investigated the incidence of the common MYH mutations in an Australian cohort of sporadic colorectal cancers, the clinicopathologica...

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Autores principales: Colebatch, A, Hitchins, M, Williams, R, Meagher, A, Hawkins, N J, Ward, R L
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360566/
https://www.ncbi.nlm.nih.gov/pubmed/17031395
http://dx.doi.org/10.1038/sj.bjc.6603421
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author Colebatch, A
Hitchins, M
Williams, R
Meagher, A
Hawkins, N J
Ward, R L
author_facet Colebatch, A
Hitchins, M
Williams, R
Meagher, A
Hawkins, N J
Ward, R L
author_sort Colebatch, A
collection PubMed
description Biallelic germline mutations in MYH are associated with colorectal neoplasms, which develop through a pathway involving somatic inactivation of APC. In this study, we investigated the incidence of the common MYH mutations in an Australian cohort of sporadic colorectal cancers, the clinicopathological features of MYH cancers, and determined whether inactivation of mismatch repair and base excision repair (BER) were mutually exclusive. The MYH gene was sequenced from lymphocyte DNA of 872 colorectal cancer patients and 478 controls. Two compound heterozygotes were identified in the cancer population and all three cancers from these individuals displayed a prominent infiltration of intraepithelial lymphocytes. In total, 11 heterozygotes were found in the cancer group and five in the control group. One tumour from an individual with biallelic germline mutation of MYH also demonstrated microsatellite instability (MSI) as a result of biallelic hypermethylation of the MLH1 promoter. Although MYH-associated cancers are rare in a sporadic colorectal population, this study shows that these tumours can develop through either a chromosomal or MSI pathway. Tumours arising in the setting of BER or mismatch repair deficiency may share a biological characteristic, which promotes lymphocytic infiltration.
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spelling pubmed-23605662009-09-10 The role of MYH and microsatellite instability in the development of sporadic colorectal cancer Colebatch, A Hitchins, M Williams, R Meagher, A Hawkins, N J Ward, R L Br J Cancer Short Communication Biallelic germline mutations in MYH are associated with colorectal neoplasms, which develop through a pathway involving somatic inactivation of APC. In this study, we investigated the incidence of the common MYH mutations in an Australian cohort of sporadic colorectal cancers, the clinicopathological features of MYH cancers, and determined whether inactivation of mismatch repair and base excision repair (BER) were mutually exclusive. The MYH gene was sequenced from lymphocyte DNA of 872 colorectal cancer patients and 478 controls. Two compound heterozygotes were identified in the cancer population and all three cancers from these individuals displayed a prominent infiltration of intraepithelial lymphocytes. In total, 11 heterozygotes were found in the cancer group and five in the control group. One tumour from an individual with biallelic germline mutation of MYH also demonstrated microsatellite instability (MSI) as a result of biallelic hypermethylation of the MLH1 promoter. Although MYH-associated cancers are rare in a sporadic colorectal population, this study shows that these tumours can develop through either a chromosomal or MSI pathway. Tumours arising in the setting of BER or mismatch repair deficiency may share a biological characteristic, which promotes lymphocytic infiltration. Nature Publishing Group 2006-11-06 2006-10-10 /pmc/articles/PMC2360566/ /pubmed/17031395 http://dx.doi.org/10.1038/sj.bjc.6603421 Text en Copyright © 2006 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Short Communication
Colebatch, A
Hitchins, M
Williams, R
Meagher, A
Hawkins, N J
Ward, R L
The role of MYH and microsatellite instability in the development of sporadic colorectal cancer
title The role of MYH and microsatellite instability in the development of sporadic colorectal cancer
title_full The role of MYH and microsatellite instability in the development of sporadic colorectal cancer
title_fullStr The role of MYH and microsatellite instability in the development of sporadic colorectal cancer
title_full_unstemmed The role of MYH and microsatellite instability in the development of sporadic colorectal cancer
title_short The role of MYH and microsatellite instability in the development of sporadic colorectal cancer
title_sort role of myh and microsatellite instability in the development of sporadic colorectal cancer
topic Short Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360566/
https://www.ncbi.nlm.nih.gov/pubmed/17031395
http://dx.doi.org/10.1038/sj.bjc.6603421
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