title: Clinicopathological significance of aberrant methylation of RARbeta2 at 3p24, RASSF1A at 3p21.3, and FHIT at 3p14.2 in patients with non-small cell lung cancer.
abstract: We investigated the clinicopathological significance of aberrant methylation of the retinoic acid receptor-beta2 (RARbeta2), RAS association domain family 1A (RASSF1A) and fragile histidine triad (FHIT) genes located on choromosome 3p in 120 patients with primary non-small cell lung cancer (NSCLC) by a methylation-specific PCR method. Aberrant methylation of these was detected in 31 (26%), 35 (29%) and 43 (36%) tumors, respectively. There was no correlation with the methylation status of any of the genes. RARbeta2 methylation was more frequently observed in patients with a smoking history (19 of 61, 31%) than in patients without one (3 of 29, 10%, P = 0.0373). RARbeta2 methylation was also preferentially observed in advanced stage NSCLC (12 of 71 (17%) in stage I, 5 of 15 (33%) in stage II, 11 of 24 (46%) in stage III, and 3 of 8 (38%) in stage IV, P = 0.0057 (stage I versus II, III,and IV)). FHIT methylation was predominantly detected in tumors with vascular invasion (21 of 44, 48%, P = 0.0703) or lymphatic permeation (28 of 59, 47%, P = 0.0115). RASSF1A methylation was more frequently observed in adenocarcinomas (28 of 72, 39%) than in squamous cell carcinomas (6 of 45, 13%, P = 0.0033). These results indicate that aberrant methylation of the candidate tumor suppressor genes on 3p plays a respective role in the pathogenesis of NSCLC.
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma 371-8511, Japan. ytomizaw@showa.gunma-u.ac.jp
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Tomizawa
authors.forename: Hironobu
authors.initials: H
authors.lastname: Iijima
authors.forename: Taisuke
authors.initials: T
authors.lastname: Nomoto
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Iwasaki
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Otani
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tsuchiya
authors.forename: Ryusei
authors.initials: R
authors.lastname: Saito
authors.forename: Kunio
authors.initials: K
authors.lastname: Dobashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakajima
authors.forename: Masatomo
authors.initials: M
authors.lastname: Mori
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000503:physiopathology*; D002893:Chromosomes, Human, Pair 3; D019175:DNA Methylation; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D018168:Receptors, Retinoic Acid / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D018168:Receptors, Retinoic Acid; D025521:Tumor Suppressor Proteins; D000099170:Bis(5'-adenosyl)triphosphatase; C411762:RASSF1 protein, human; C082925:retinoic acid receptor beta