Relationship of Ras association domain family 1 methylation and K-ras mutation in primary non-small cell lung cancer.
Recently, several groups have reported that Ras association domain family 1 (RASSF1A) interacts with Ras and mediates Ras-dependent apoptosis. However, the mechanism by which RASSF1A plays a role as a tumor suppressor in human cancer is unclear. In this study, we investigated the relationship between the RASSF1A methylation and K-ras mutation and their effects on patient's survival in 242 primary non-small cell lung cancers (NSCLCs) to understand the role of RASSF1A in Ras-mediated oncogenic transformation. RASSF1A methylation was not found to be associated with the K-ras mutation in NSCLCs (P = 0.37). For patients with stage I adenocarcinoma, those with RASSF1A methylation and K-ras mutation had a poorer prognosis than those with either RASSF1A methylation or K-ras mutation (P = 0.001). In stage II-III adenocarcinoma patients, the median survival of those with RASSF1A methylation and K-ras mutation was 9 months, and this was poorer than that of those with either RASSF1A methylation or K-ras mutation (P = 0.001). The hazard of failure for those with RASSF1A methylation and K-ras mutation was approximately 2.94 times higher compared with that of those with neither K-ras mutation nor RASSF1A methylation (95% confidence interval = 1.67-9.42; P = 0.01). Our results suggest that RASSF1A methylation and K-ras mutation are not mutually exclusive in NSCLC. In addition, RASSF1A methylation, in combination with K-ras mutation, may have an adverse synergistic effect on patient's survival in NSCLCs.
Kim
Duk-Hwan
DH
Center for Genomics Research, Samsung Biomedical Research Institute, Room B155, #50 Ilwon-dong, Kangham-ku, 135-710 Seoul, Korea. dukhwan@samsung.co.kr
Kim
Jin Seuk
JS
Park
Jung-Ho
JH
Lee
Suk Kyoo
SK
Ji
Yong-Ick
YI
Kwon
Young Mi
YM
Shim
Young Mog
YM
Han
Joungho
J
Park
Joobae
J
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D003062:Codon; D019175:DNA Methylation; D005260:Female; D016147:Genes, Tumor Suppressor; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D015996:Survival Rate; D025521:Tumor Suppressor Proteins
D003062:Codon; D009363:Neoplasm Proteins; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins