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MAL promoter hypermethylation as a novel prognostic marker in gastric cancer.

Buffart TE, Overmeer RM, Steenbergen RD, Tijssen M, van Grieken NC, Snijders PJ, Grabsch HI, van de Velde CJ, Carvalho B, Meijer GA - Br. J. Cancer (2008)

Bottom Line: 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.Two regions within the MAL promoter (M1 and M2) were analysed.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).

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.

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=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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Kaplan–Meier survival analysis of 179 patients with primary gastric cancers assessed for the methylation status of the M2 region (−92 to −7 bp) within the MAL promoter. Patients with primary gastric cancers methylated for the M2 promoter region (n=143) showed a significantly better survival compared to patients (n=36) with gastric cancers without M2 promoter methylation (P=0.03; log rank=4.96). The number of patients who died of gastric cancer (events) is 70 and 22, respectively.
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fig2: Kaplan–Meier survival analysis of 179 patients with primary gastric cancers assessed for the methylation status of the M2 region (−92 to −7 bp) within the MAL promoter. Patients with primary gastric cancers methylated for the M2 promoter region (n=143) showed a significantly better survival compared to patients (n=36) with gastric cancers without M2 promoter methylation (P=0.03; log rank=4.96). The number of patients who died of gastric cancer (events) is 70 and 22, respectively.

Mentions: Follow-up data was available for 200 out of 202 patients. Only patients without distant metastasis at the time of surgery (M0) were included, leaving 179 patients for the survival analysis. Patients with a gastric carcinoma methylated for the M2 promoter region had a significantly better survival compared with patients with tumours unmethylated for the M2 promoter region (P=0.03) (Figure 2). No significant correlation was found between M2 promoter methylation and age or gender of the patient, histological type of the tumour, T-stage and N-stage (Table 2). In addition, no significant correlation between M1 promoter methylation status and clinicopathological characteristics, including survival, was found.


MAL promoter hypermethylation as a novel prognostic marker in gastric cancer.

Buffart TE, Overmeer RM, Steenbergen RD, Tijssen M, van Grieken NC, Snijders PJ, Grabsch HI, van de Velde CJ, Carvalho B, Meijer GA - Br. J. Cancer (2008)

Kaplan–Meier survival analysis of 179 patients with primary gastric cancers assessed for the methylation status of the M2 region (−92 to −7 bp) within the MAL promoter. Patients with primary gastric cancers methylated for the M2 promoter region (n=143) showed a significantly better survival compared to patients (n=36) with gastric cancers without M2 promoter methylation (P=0.03; log rank=4.96). The number of patients who died of gastric cancer (events) is 70 and 22, respectively.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2600687&req=5

fig2: Kaplan–Meier survival analysis of 179 patients with primary gastric cancers assessed for the methylation status of the M2 region (−92 to −7 bp) within the MAL promoter. Patients with primary gastric cancers methylated for the M2 promoter region (n=143) showed a significantly better survival compared to patients (n=36) with gastric cancers without M2 promoter methylation (P=0.03; log rank=4.96). The number of patients who died of gastric cancer (events) is 70 and 22, respectively.
Mentions: Follow-up data was available for 200 out of 202 patients. Only patients without distant metastasis at the time of surgery (M0) were included, leaving 179 patients for the survival analysis. Patients with a gastric carcinoma methylated for the M2 promoter region had a significantly better survival compared with patients with tumours unmethylated for the M2 promoter region (P=0.03) (Figure 2). No significant correlation was found between M2 promoter methylation and age or gender of the patient, histological type of the tumour, T-stage and N-stage (Table 2). In addition, no significant correlation between M1 promoter methylation status and clinicopathological characteristics, including survival, was found.

Bottom Line: 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.Two regions within the MAL promoter (M1 and M2) were analysed.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).

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.

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=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.

Show MeSH
Related in: MedlinePlus