Open AccessPromoter hypermethylation of tumor suppressor and tumor‐related genes in non‐small cell lung cancers
Author(s) -
Yanagawa Naoki,
Tamura Gen,
Oizumi Hiroyuki,
Takahashi Nobumasa,
Shimazaki Yasuhisa,
Motoyama Teiichi
Publication year - 2003
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2003.tb01487.x
Subject(s) - methylation , cancer research , dna methylation , lung cancer , tumor suppressor gene , cpg site , carcinogenesis , biology , adenocarcinoma , cancer , cell , gene , microbiology and biotechnology , pathology , medicine , gene expression , genetics
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.