Limits...
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.

Show MeSH

Related in: MedlinePlus

Receiver operator characteristics of (A) M1 promoter methylation and (B) M2 promoter methylation in 202 gastric cancers and 22 normal gastric mucosa samples (FFPE samples only), assuming that normal gastric mucosae are unmethylated and gastric carcinomas are methylated. Chosen cutoff levels for methylation were 95 and 22 for M1 and M2 promoter regions, respectively. This yielded a specificity of 100% for both promoter regions and a sensitivity of 71% for M1 promoter region and 80% for the M2 promoter region.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2600687&req=5

fig1: Receiver operator characteristics of (A) M1 promoter methylation and (B) M2 promoter methylation in 202 gastric cancers and 22 normal gastric mucosa samples (FFPE samples only), assuming that normal gastric mucosae are unmethylated and gastric carcinomas are methylated. Chosen cutoff levels for methylation were 95 and 22 for M1 and M2 promoter regions, respectively. This yielded a specificity of 100% for both promoter regions and a sensitivity of 71% for M1 promoter region and 80% for the M2 promoter region.

Mentions: The chosen cutoff values of methylation for the M1 and M2 promoter regions, based on the ROC curve analysis, were ratios of relative methylated DNA quantities of M1/β-actin × 1000 and M2/β-actin × 1000 above 95 and 22, respectively, yielding a specificity of 100% for both promoter regions and a sensitivity of 71 and 80% for M1 and M2 promoter regions, respectively. ROC curves for both M1 and M2 promoter regions are shown in Figure 1.


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)

Receiver operator characteristics of (A) M1 promoter methylation and (B) M2 promoter methylation in 202 gastric cancers and 22 normal gastric mucosa samples (FFPE samples only), assuming that normal gastric mucosae are unmethylated and gastric carcinomas are methylated. Chosen cutoff levels for methylation were 95 and 22 for M1 and M2 promoter regions, respectively. This yielded a specificity of 100% for both promoter regions and a sensitivity of 71% for M1 promoter region and 80% for the M2 promoter region.
© Copyright Policy
Related In: Results  -  Collection

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

fig1: Receiver operator characteristics of (A) M1 promoter methylation and (B) M2 promoter methylation in 202 gastric cancers and 22 normal gastric mucosa samples (FFPE samples only), assuming that normal gastric mucosae are unmethylated and gastric carcinomas are methylated. Chosen cutoff levels for methylation were 95 and 22 for M1 and M2 promoter regions, respectively. This yielded a specificity of 100% for both promoter regions and a sensitivity of 71% for M1 promoter region and 80% for the M2 promoter region.
Mentions: The chosen cutoff values of methylation for the M1 and M2 promoter regions, based on the ROC curve analysis, were ratios of relative methylated DNA quantities of M1/β-actin × 1000 and M2/β-actin × 1000 above 95 and 22, respectively, yielding a specificity of 100% for both promoter regions and a sensitivity of 71 and 80% for M1 and M2 promoter regions, respectively. ROC curves for both M1 and M2 promoter regions are shown in Figure 1.

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