title: Methylation profile in tumor and sputum samples of lung cancer patients detected by spiral computed tomography: a nested case-control study.
abstract: We evaluated the aberrant promoter methylation profile of a panel of 3 genes in DNA from tumor and sputum samples, in view of a complementary approach to spiral computed tomography (CT) for early diagnosis of lung cancer. The aberrant promoter methylation of RARbeta2, p16(INK4A) and RASSF1A genes was evaluated by methylation-specific PCR in tumor samples of 29 CT-detected lung cancer patients, of which 18 had tumor-sputum pairs available for the analysis, and in the sputum samples from 112 cancer-free heavy smokers enrolled in a spiral CT trial. In tumor samples from 29 spiral CT-detected patients, promoter hypermethylation was identified in 19/29 (65.5%) cases for RARbeta2, 12/29 (41.4%) for p16(INK4A) and 15/29 (51.7%) for RASSF1A. Twenty-three of twenty-nine (79.3%) samples of the tumors exhibited methylation in at least 1 gene. In the sputum samples of 18 patients, methylation was detected in 8/18 (44.4%) for RARbeta2 and 1/18 (5%) for both RASSF1A and p16(INK4A). At least 1 gene was methylated in 9/18 (50%) sputum samples. Promoter hypermethylation in sputum from 112 cancer-free smokers was observed in 58/112 (51.7%) for RARbeta2 and 20/112 (17.8%) for p16, whereas methylation of the RASSF1A gene was found in only 1/112 (0.9%) sputum sample. Our study indicates that a high frequency of hypermethylation for RARbeta2, p16(INK4A) and RASSF1A promoters is present in spiral CT-detected tumors, whereas promoter hypermethylation of this panel of genes in uninduced sputum has a limited diagnostic value in early lung cancer detection.
authors.affiliation: Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Rosalia
authors.initials: R
authors.lastname: Cirincione
authors.forename: Carla
authors.initials: C
authors.lastname: Lintas
authors.forename: Davide
authors.initials: D
authors.lastname: Conte
authors.forename: Luigi
authors.initials: L
authors.lastname: Mariani
authors.forename: Luca
authors.initials: L
authors.lastname: Roz
authors.forename: Antonio Maurizio
authors.initials: AM
authors.lastname: Vignola
authors.forename: Ugo
authors.initials: U
authors.lastname: Pastorino
authors.forename: Gabriella
authors.initials: G
authors.lastname: Sozzi
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics; D012907:Smoking; D013183:Sputum / Q000378:metabolism*; D036542:Tomography, Spiral Computed; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; C411762:RASSF1 protein, human; D018168:Receptors, Retinoic Acid; D025521:Tumor Suppressor Proteins; C082925:retinoic acid receptor beta