title: Aberrant promoter methylation in Chinese patients with non-small cell lung cancer: patterns in primary tumors and potential diagnostic application in bronchoalevolar lavage.
abstract: This study was aimed at defining patterns of aberrant gene methylation in non-small cell lung cancer (NSCLC) in Chinese patients and its use in detecting cancer cells in bronchoalveolar lavage (BAL). The methylation-specific PCR (MSP) was used to study methylation of the p16, retinoic acid receptor-beta (RARbeta), death-associated protein (DAP) kinase, and O(6)-methylguanine-DNA-methyltransferase (MGMT) genes in 75 NSCLCs [44 adenocarcinomas and 31 squamous cell carcinomas (SCCs)] and 68 BALs from suspected lung cancers. More females had adenocarcinoma than SCC (11 of 44 versus 2 of 31, P = 0.04). Aberrant methylation in at least one gene was found in 63 of 75 (84%) NSCLCs. p16, RARbeta, DAP kinase, and MGMT methylation was similar in adenocarcinoma and SCC. However, females with NSCLC showed more frequent p16 methylation than males (12 of 13 versus 36 of 62, P = 0.02), because of more frequent p16 methylation in female adenocarcinomas (10 of 11 versus 17 of 33, P = 0.02). This sexual difference was not observed in RARbeta, DAP kinase, and MGMT. At 92%, the frequency of p16 methylation in Chinese female NSCLC is one of the highest known. For BAL, MSP and cytological analysis showed concordant and discordant results in 25 of 68 and 43 of 68 samples. Of 41 MSP+/cytology- cases, 35 were eventually shown to have malignant lung lesions, 4 were at high risk but had no evidence of lung cancer, and 2 were lost to follow-up. There were two MSP-/cytology+ cases. Frequent gene methylations were seen in Chinese NSCLC patients. More frequent p16 methylation was seen in female patients. MSP is a useful molecular adjunct for cancer cell detection in BAL samples.
authors.affiliation: University Department of Medicine, Queen Mary Hospital, Hong Kong.
authors.forename: Eunice C
authors.initials: EC
authors.lastname: Chan
authors.forename: Shui Y
authors.initials: SY
authors.lastname: Lam
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Tsang
authors.forename: Bing
authors.initials: B
authors.lastname: Lam
authors.forename: James C M
authors.initials: JC
authors.lastname: Ho
authors.forename: Kin H
authors.initials: KH
authors.lastname: Fu
authors.forename: Wah K
authors.initials: WK
authors.lastname: Lam
authors.forename: Yok L
authors.initials: YL
authors.lastname: Kwong
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D051017:Apoptosis Regulatory Proteins; D018893:Bronchoalveolar Lavage; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D002681:China / Q000453:epidemiology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000378:metabolism; D064550:Death-Associated Protein Kinases; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011446:Prospective Studies; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D012307:Risk Factors; D012680:Sensitivity and Specificity; D015996:Survival Rate
chemical_list: D051017:Apoptosis Regulatory Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D018168:Receptors, Retinoic Acid; D019853:O(6)-Methylguanine-DNA Methyltransferase; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases