MAL promoter hypermethylation as a novel prognostic marker in gastric cancer

被引：56
作者：
Buffart, T. E. [1 ]
Overmeer, R. M. [1 ]
Steenbergen, R. D. M. [1 ]
Tijssen, M. [1 ]
van Grieken, N. C. T. [1 ]
Snijders, P. J. F. [1 ]
Grabsch, H. I. [2 ]
van de Velde, C. J. H. [3 ]
Carvalho, B. [1 ]
Meijer, G. A. [1 ]
机构：
[1] Vrije Univ Amsterdam Med Ctr, Dept Pathol, NL-1007 MB Amsterdam, Netherlands
[2] Univ Leeds, Leeds Inst Mol Med, Leeds, W Yorkshire, England
[3] Leiden Univ, Med Ctr, Dept Surg, Leiden, Netherlands
来源：
BRITISH JOURNAL OF CANCER | 2008年 / 99卷 / 11期
关键词：
gastric cancer; promoter hypermethylation; prognostic marker; MAL;
D O I：
10.1038/sj.bjc.6604777
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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.
引用
收藏
页码：1802 / 1807
页数：6
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