Aberrant promoter methylation in sputum and serum for lung cancer detection

Key to the early detection of lung cancer is the development of biomarkers that are found early in disease development and can be detected in biological fluids prior to advanced disease. We have been examining genes inactivated by aberrant gene promoter hypermethylation as candidate biomarkers for early detection of lung cancer. We have shown that aberrant hypermethylation of the p16 gene occurs at the earliest stages of squamous cell carcinoma and increases in frequency during disease progression. Furthermore, methylation of the p16 and O⁶-methylguanine-DNA methyltransferase promoters was detected in DNA from sputum in 100 % of patients with squamous cell carcinoma up to 3 years before clinical diagnosis. In addition, promoter methylation of p16, O⁶-methylguanine-DNA methyltransferase, or death-associated protein kinase was detected in the serum from 70% of patients whose non-small cell lung cancer contained the same methylation change. Taken together, these findings indicate that promoter methylation in sputum and serum could serve as a powerful approach to population-based screening for the detection of lung cancer.