Promoter hypermethylation of tumor suppressor and tumor-related genes in non-small cell lung cancers.
Aberrant methylation of promoter CpG islands is known to be a major inactivation mechanism of tumor suppressor and tumor-related genes. To determine the clinicopathological significance of gene promoter methylation in non-small cell lung cancer (NSCLC), we examined the promoter methylation status of the APC, DAP-kinase, E-cadherin, GSTP1, hMLH1, p16, RASSF1A and RUNX3 genes in 75 NSCLCs and corresponding non-neoplastic lung tissues by methylation-specific PCR (MSP). The frequencies of methylation in NSCLCs and corresponding non-neoplastic lung tissues were: 37% (28 of 75) and 48% (36 of 75) for APC, 28% (21 of 75) and 13% (10 of 75) for DAP-kinase, 29% (22 of 75) and 15% (11 of 75) for E-cadherin, 1% (1 of 75) and 0% (0 of 75) for GSTP1, 7% (5 of 75) and 0% (0 of 75) for hMLH1, 31% (23 of 75) and 0% (0 of 75) for p16, 43% (32 of 75) and 4% (3 of 75) for RASSF1A, and 20% (15 of 75) and 3% (2 of 75) for RUNX3, respectively. Methylation of p16 was more frequent in squamous cell carcinomas than in adenocarcinomas (P < 0.05), and was associated with tobacco smoking (P < 0.05). On the contrary, methylation of APC and RUNX3 was more frequent in adenocarcinomas than in squamous cell carcinomas (P < 0.05). Thus, a different set of genes is thought to undergo promoter methylation, which leads to the development of different histologies. In addition, methylation of p16, RASSF1A and RUNX3 was mostly cancer-specific (P < 0.05), and may be utilized as a molecular diagnostic marker of NSCLCs.
Yanagawa
Naoki
N
Department of Pathology, Yamagata University School of Medicine, Yamagata 990-9585, Japan.
Tamura
Gen
G
Oizumi
Hiroyuki
H
Takahashi
Nobumasa
N
Shimazaki
Yasuhisa
Y
Motoyama
Teiichi
T
D000328:Adult; D000367:Age Factors; D000368:Aged; D051017:Apoptosis Regulatory Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D019175:DNA Methylation; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics* / Q000302:isolation & purification; D064550:Death-Associated Protein Kinases; D017491:Genes, APC; D016147:Genes, Tumor Suppressor; D006801:Humans; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012016:Reference Values
D051017:Apoptosis Regulatory Proteins; D017931:DNA Primers; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases