MAL promoter hypermethylation as a novel prognostic marker in gastric cancer

• Published in: British journal of cancer Vol. 99; no. 11; pp. 1802 - 1807
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02-12-2008; Nature Publishing Group
• Subjects: Aged; Aged, 80 and over; Archives & records; Biological and medical sciences; Biomarkers, Tumor - genetics; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell cycle; Cervical cancer; DNA Methylation; Drug Resistance; Epidemiology; Female; Gastric cancer; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression; Genes; Genes, Tumor Suppressor; Humans; Kaplan-Meier Estimate; Male; Medical prognosis; Medical research; Medical sciences; Membrane Transport Proteins - biosynthesis; Membrane Transport Proteins - genetics; Middle Aged; Molecular Medicine; Myelin and Lymphocyte-Associated Proteolipid Proteins; Myelin Proteins - biosynthesis; Myelin Proteins - genetics; Oncology; Pathogenesis; Pathology; Penicillin; Prognosis; Promoter Regions, Genetic; Proteolipids - biosynthesis; Proteolipids - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; ROC Curve; Stomach Neoplasms - genetics; Stomach Neoplasms - mortality; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Translational Therapeutics; Tumors; Netherlands; MAL; prognostic marker; gastric cancer; promoter hypermethylation; Prognosis; Transcription promoter; Biological marker; Malignant tumor; Stomach cancer; Cancerology; Digestive diseases; Cancer; Gastric disease
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6604777

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.