|Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥2,700,000 (Direct Cost: ¥2,700,000)
Despite recent advances in cancer therapy, lung cancer remains one of the major causes of cancer death worldwide. Therefore, precise methods for prediction of prognosis are required for optimal selection from among the available modalities of lung cancer therapy. In this study, DNA methylation profile of tumor and normal tissue in lung cancer was analyzed to make use of the profile for personalized medicine in the treatment of this disease.
The method of real-time methylation specific PCR (MethyLight) from formalin-fixed paraffin-embedded tissue was established. DNA was isolated from 350 matched tumor and adjacent normal tissue, followed by MethyLight assay on p16, hMLH1, APC, MGMT, DAPK, MYOD1, TIMP3. Frequencies of the hypermethylation in tumor (T) and normal tissue (N) were as follows : p16(T), 14.1% ; p16(N), 1.8% ; hMLH1(T), 0.7% ; hMLH1(N), 0% ; APC(T), 24.8% ; APC(N), 8.8% ; MGMT(T), 67.2% ; MGMT(N), 87.5 ; DAPK(T), 1.6% ; DAPK(N), 3.6% ; MYOD1(T), 42.2% ; MYOD1(N), 34.4% ; TIMP3(T), 3.1% ; TIMP3(N), 3.6%. Hypermethylation of p16 was more frequent in male and squamous cell carcinoma. Contrary, APC hypermethylation was more frequent in adenocarcinoma. In survival analysis with 240 patients, hypermethylation of p16 and MYOD1 were significant poor prognostic factor.
These results suggest that the DNA methylation profile in lung cancer is useful for personalized medicine in the treatment of lung cancer patients.