Aberrant Methylation of p16 Tumor Suppressor Gene and Death-Associated Protein Kinase in Non-Small Cell Lung Carcinoma

Kim, Yun Seong; Lee, Min Ki; Jung, Kyung Sik; Kim, Ki Uk; Kim, Young Dae; Lee, Hyung Ryul; Lee, Chang Hoon; Seok, Ju Won; Kim, Yong Ki; Jun, Eun Sook; Choi, Young Min; Rha, Seo Hee; Park, Soon Kew

Abstract

BACKGROUND
The p16INK4a (p16) tumor suppressor gene is frequently inactivated in human non-small cell lung cancers (NSCLCs), predominantly through homozygous deletion or in association with aberrant promotor hypermethylation. Death-associated protein kinase (DAPK) gene influences interferon Î³-induced apoptotic cell death and has important role in metastasis of lung cancer in animal model. Hypermethylation of promoter region of DAP kinase gene may suppress the expression of this gene.
METHODS
This study was performed to investigate the aberrant methylation of p16 or DAP kinase in 35 resected primary NSCLCs by methylation-specific PCR (MSP), and demonstrated frequency, diagnostic value and clinical implication of aberrant methylation of two genes.
RESULTS
Thirty-two cases were male patients, and 3 cases were female patients with an average age was 57.8±10.5 years. The histologic types of lung cancer were 22 of squamous cell carcinoma, 12 of adenocarcinoma, 1 of large cell carcinoma. Pathologic stages were 11 cases of stage I(1 IA,10 IB), 13 cases of stage II (1 IIA, 12 IIB), and 11 cases of stage III(9 IIIA, 2 IIIB). Regarding for the cancer tissue, p16 aberrant methylation was noted in 13 case of 33 cases (39.4%), DAP kinase in 21 cases of 35 cases (60%). Age over 55 year was associated with p16 aberrant methylation significantly (p<0.05). Methylation status of two genes was not different by smoking history, histologic type, size of tumor, lymph node metastasis and disease progression of lung cancer. There was no correlation between p16 and DAP kinase hypermethylation.
CONCLUSION
This investigation demonstrates that aberrant methylation of p16 tumor suppressor gene or DAP kinase showed relatively high frequency (74.3%) in NSCLCs, and that these genes could be a biologic marker for early detection of lung cancer.