Methylation profile in tumor and sputum samples of lung cancer patients detected by spiral computed tomography: a nested case-control study

Int J Cancer. 2006 Mar 1;118(5):1248-53. doi: 10.1002/ijc.21473.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Case-Control Studies
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • DNA Methylation*
  • DNA, Neoplasm / genetics
  • DNA, Neoplasm / metabolism*
  • Female
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Promoter Regions, Genetic / genetics
  • Receptors, Retinoic Acid / genetics
  • Smoking
  • Sputum / metabolism*
  • Tomography, Spiral Computed
  • Tumor Suppressor Proteins / genetics


  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Neoplasm
  • RASSF1 protein, human
  • Receptors, Retinoic Acid
  • Tumor Suppressor Proteins
  • retinoic acid receptor beta