The analysis of methylation, acetylation and mutation of the tumor suppressor gene in the lung cancer.

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 17591488
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Tokyo Medical University
• Principal Investigator: MIYAJIMA Kuniharu Tokyo Medical University, Surgery I, Assistant Professor, 医学部, 助手 (80372952)
• Co-Investigator(Kenkyū-buntansha): OHIRA Tatso Tokyo Medical University, Surgery I, Assistant Professor, 医学部, 講師 (40317847) ; SUGA Yasuhiro Tokyo Medical University, Surgery I, Assistant Professor, 医学部, 助手 (40408258) ; HONDA Hidetoshi Tokyo Medical University, Surgery I, Assistant Professor, 医学部, 助手 (60349503) ; HIRANO Takashi Tokyo Medical University, Surgery I, Associate Professor, 医学部, 助教授 (30238381) ; KATO Harubumi Tokyo Medical University, Surgery I, Professor, 医学部, 教授 (20074768)
• Project Period (FY): 2005 – 2006
• Keywords: NSCLC / tumor suppressor gene / methylation / early diagnosis / EGFR / mutation / gefitinib

Research Abstract

Purpose : In this study, we investigated the clinicopathological significances of RASSF1A methylation in the development and/or progression of small-sized (less than 2.0cm) lung adenocarcinoma.
Methods : Surgically resected specimens from 77 cases of small-sized (less than 2.0cm) adenocarcinoma. Aberrant promoter methylation was examined using methylation-specific PCR.
Results : 1. Twenty-five of 77 (32.5%) tumors showed RASSF1 A methylation.
2.RASSF1 A methylation was dominantly detected in smoker (p <0.03).
3.RASSF1 A methylation correlated with adverse survival by univariate analysis (p <0.005) as well as multivariate analysis (p=0.0062).
Conclusion : 1. RASSF1 A methylation was significantly related to unfavorable prognosis in small-sized lung adenocarcinoma.
2.Epigenetic inactivation of RASSF1A plays an important role in the progression of small-sized lung adenocarcinoma, and that RASSF1A hypermethylation appears to be a useful molecular marker for the prognosis of patients with small-s ized lung adenocarcinoma.
Introduction : We examined whether aberrant p16 and ER methylation might also be found in the blood of patients with NSCLC using real-time PCR.
Materials and Methods : Blood samples Were obtained from 95 patients with non-small cell lung cancer and 32 normal controls. We tested 127 samples to determine the quantity of p16 and ER promoter methylation using real-time PCR.
Results : About p16 and ER, there was a statistical difference between NSCLC patients and normal control (p<0.003, p<0.001). Then there is some correlation between p16 promoter methylation and aging
Conclusion : p16 and ER promoter rmethylation in blood using real time PCR appears useful for lung cancer diagnosis and there is some possibility to be biomarkers for early detection of lung cancer.
Gefitinib, an EGFR tyrosine kinase inhibitor, was approved in Japan in 2002 for the treatment of inoperable or recurrent NSCLC. We compared the molecular characterization of an established NSCLC cell line with clinical NSCLC samples obtained by operation.
We detected the mutation of EGFR with paraffin embedded sample. The samples were obtained from the patients who received operation for lung cancer in our department. Number of adenocarcinoma patients is 93. The result of the sequence is 44/93 (47.3%) adenocarcinoma showed mutations.