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MAL promoter hypermethylation as a novel prognostic marker in gastric cancer

T-lymphocyte maturation associated protein, MAL, has been described as a tumour-suppressor gene with diagnostic value in colorectal and oesophageal cancers, and can be inactivated by promoter hypermethylation. The aim of this study was to analyse the prevalence of MAL promoter hypermethylation and t...

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Autores principales: Buffart, T E, Overmeer, R M, Steenbergen, R D M, Tijssen, M, van Grieken, N C T, Snijders, P J F, Grabsch, H I, van de Velde, C J H, Carvalho, B, Meijer, G A
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2600687/
https://www.ncbi.nlm.nih.gov/pubmed/19002170
http://dx.doi.org/10.1038/sj.bjc.6604777
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author Buffart, T E
Overmeer, R M
Steenbergen, R D M
Tijssen, M
van Grieken, N C T
Snijders, P J F
Grabsch, H I
van de Velde, C J H
Carvalho, B
Meijer, G A
author_facet Buffart, T E
Overmeer, R M
Steenbergen, R D M
Tijssen, M
van Grieken, N C T
Snijders, P J F
Grabsch, H I
van de Velde, C J H
Carvalho, B
Meijer, G A
author_sort Buffart, T E
collection PubMed
description T-lymphocyte maturation associated protein, MAL, has been described as a tumour-suppressor gene with diagnostic value in colorectal and oesophageal cancers, and can be inactivated by promoter hypermethylation. The aim of this study was to analyse the prevalence of MAL promoter hypermethylation and the association with mRNA expression in gastric cancers and to correlate methylation status to clinicopathological data. Bisulphite-treated DNA isolated from formalin-fixed and paraffin-embedded samples of 202 gastric adenocarcinomas and 22 normal gastric mucosae was subjected to real-time methylation-specific PCR (Q-MSP). Two regions within the MAL promoter (M1 and M2) were analysed. In addition, 17 frozen gastric carcinomas and two gastric cancer cell lines were analysed both by Q-MSP and real-time RT–PCR. Methylation of M1 and M2 occurred in 71 and 80% of the gastric cancers, respectively, but not in normal gastric mucosa tissue. Hypermethylation of M2, but not M1, correlated with significantly better disease-free survival in a univariate (P=0.03) and multivariate analysis (P=0.03) and with downregulation of expression (P=0.01). These results indicate that MAL has a putative tumour-suppressor gene function in gastric cancer, and detection of promoter hypermethylation may be useful as a prognostic marker.
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spelling pubmed-26006872009-12-03 MAL promoter hypermethylation as a novel prognostic marker in gastric cancer Buffart, T E Overmeer, R M Steenbergen, R D M Tijssen, M van Grieken, N C T Snijders, P J F Grabsch, H I van de Velde, C J H Carvalho, B Meijer, G A Br J Cancer Translational Therapeutics T-lymphocyte maturation associated protein, MAL, has been described as a tumour-suppressor gene with diagnostic value in colorectal and oesophageal cancers, and can be inactivated by promoter hypermethylation. The aim of this study was to analyse the prevalence of MAL promoter hypermethylation and the association with mRNA expression in gastric cancers and to correlate methylation status to clinicopathological data. Bisulphite-treated DNA isolated from formalin-fixed and paraffin-embedded samples of 202 gastric adenocarcinomas and 22 normal gastric mucosae was subjected to real-time methylation-specific PCR (Q-MSP). Two regions within the MAL promoter (M1 and M2) were analysed. In addition, 17 frozen gastric carcinomas and two gastric cancer cell lines were analysed both by Q-MSP and real-time RT–PCR. Methylation of M1 and M2 occurred in 71 and 80% of the gastric cancers, respectively, but not in normal gastric mucosa tissue. Hypermethylation of M2, but not M1, correlated with significantly better disease-free survival in a univariate (P=0.03) and multivariate analysis (P=0.03) and with downregulation of expression (P=0.01). These results indicate that MAL has a putative tumour-suppressor gene function in gastric cancer, and detection of promoter hypermethylation may be useful as a prognostic marker. Nature Publishing Group 2008-12-02 2008-11-11 /pmc/articles/PMC2600687/ /pubmed/19002170 http://dx.doi.org/10.1038/sj.bjc.6604777 Text en Copyright © 2008 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 Translational Therapeutics
Buffart, T E
Overmeer, R M
Steenbergen, R D M
Tijssen, M
van Grieken, N C T
Snijders, P J F
Grabsch, H I
van de Velde, C J H
Carvalho, B
Meijer, G A
MAL promoter hypermethylation as a novel prognostic marker in gastric cancer
title MAL promoter hypermethylation as a novel prognostic marker in gastric cancer
title_full MAL promoter hypermethylation as a novel prognostic marker in gastric cancer
title_fullStr MAL promoter hypermethylation as a novel prognostic marker in gastric cancer
title_full_unstemmed MAL promoter hypermethylation as a novel prognostic marker in gastric cancer
title_short MAL promoter hypermethylation as a novel prognostic marker in gastric cancer
title_sort mal promoter hypermethylation as a novel prognostic marker in gastric cancer
topic Translational Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2600687/
https://www.ncbi.nlm.nih.gov/pubmed/19002170
http://dx.doi.org/10.1038/sj.bjc.6604777
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