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Vol.47 No.7 contents Japanese/English

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Article in Japanese

- The 21st Lung Cancer Workshop -

Molecular Classification of Lung Adenocarcinoma by Genetic Alteration Profiling

Tatsuhiro Shibata1
1Cancer Genomics Project, National Cancer Center Research Institute, Japan

Objective and Methods. Lung cancer is one of the most lethal and increasing cancer world-wide. Lung cancer is composed of a wide range of distinct histological subtypes (small cell lung carcinoma, adenocarcinoma, squamous cell carcinoma and large cell neuroendocrine carcinoma), however, the overall genetic alterations of these tumors remain unclear. To analyze the genetic alterations of lung adenocarcinoma in a genome-wide way, we employed laser-capture microdissection of cancer cells and array CGH focusing on 800 chromosomal loci containing cancer related gene. Results. We analyzed 55 primary lung adenocarcinoma cases. We identified a large number of chromosomal numerical alterations including frequent amplifications on 7p12, 11q13, 12q14-15 and 17q12 and 2 homozygous deletions on 9p21 and 1 on 8p23. Unsupervised hierarchical clustering analysis of multiple alterations revealed 3 sub-groups of lung adenocarcinoma that were characterized by the accumulation of distinct genetic alterations and associated with smoking history, gender and the frequency of EGFR (Epidermal Growth Factor Receptor) mutation. The mutation status of EGFR was significantly associated with specific genetic alterations. Conclusion. Our results suggest that there exist multiple molecular-carcinogenesis pathways in lung adenocarcinoma which may associate with smoking habits and gender. Genetic cancer profiling will reveal previously uncharacterized genetic heterogeneity of cancer and be beneficial in estimating patients' prognosis and discovering novel cancer related genes including therapeutic targets.
key words: Lung adenocarcinoma, Array-based comparative genomic hybridization, Epidermal growth factor receptor, Genetic profiling

JJLC 47 (7): 905-908, 2007

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