MAL promoter hypermethylation as a novel prognostic marker in gastric cancer

Abstract

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 ¼ 0.03) and multivariate analysis (P ¼ 0.03) and with downregulation of expression (P ¼ 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.

MAL and TMEM220 are novel DNA methylation markers in human gastric cancer

“…These findings agree with predictions made in our previous study (Figure 2a). To date, several studies have reported MAL gene methylation and mRNA-expression patterns in various cancers such as oral, breast, colon, and GC (Lind et al, 2008, Pal et al, 2012, Horne et al, 2009, Buffart et al, 2008. Buffart et al found an association between mRNA-expression levels and the methylation status of the MAL promoter region (Buffart et al, 2008).…”

Quantitative analysis of promoter methylation of the EDNRB gene in gastric cancer

“…Gene silencing by promoter hypermethylation has been described in gastric cancer for multiple genes, including CDH1, which is involved in cell adhesion, and hMLH1, which is associated with DNA mismatch repair and the cell cycle regulator p16 [8][9][10]. In addition, promoter hypermethylation of MAL has been shown to be an independent prognostic marker for gastric cancer [11].…”

Analysis of Promoter CpG Island Hypermethylation in Cancer: Location, Location, Location!

“…For example, two regions within the MAL promoter were analyzed for methylation in gastric cancer samples. Hypermethylation of both regions occurred in 71% and 80%, respectively; however, only methylation at the region closest to the TSS was correlated with a better disease-free survival (31). In addition, increased expression of MAL in serous ovarian cancer patients with a poor prognosis is associated with decreased methylation of a specific region of the MAL promoter (40).…”