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Methylation profile in tumor and sputum samples of lung cancer patients detected by spiral computed tomography: A nested case–control study
Author(s) -
Cirincione Rosalia,
Lintas Carla,
Conte Davide,
Mariani Luigi,
Roz Luca,
Vignola Antonio Maurizio,
Pastorino Ugo,
Sozzi Gabriella
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21473
Subject(s) - sputum , methylation , lung cancer , dna methylation , promoter , cancer , pathology , spiral computed tomography , medicine , cancer research , biology , gene , microbiology and biotechnology , computed tomography , gene expression , radiology , tuberculosis , genetics
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 RAR β 2 , 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 RAR β 2 , 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 RAR β 2 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 RAR β 2 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 RAR β 2 , 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. © 2005 Wiley‐Liss, Inc.