Study on molecular procedures developing oncogene fusion-positive lung cancer

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293200
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: National Cancer Center Japan
• Principal Investigator: Takashi Kohno 国立研究開発法人国立がん研究センター, その他部局等, その他 (80280783)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 遺伝子融合 / 肺がん / 非相同末端結合 / RET / 分子標的治療 / 遺伝子多型

Outline of Final Research Achievements

The purpose of this study was to elucidate molecular procedures for oncogene fusion and carcinogenic pathways developing oncogene fusion positive lung cancer. The driver fusion cases showed a distinct profile with smaller numbers of non-synonymous mutations in cancer-related genes, indicating that lung adenocarvinomas (LADCs) with ALK, RET, and ROS1 fusions develop exclusively via their dependence on these oncogene fusions. The presence of such few alterations beyond the fusions supports the use of monotherapy with tyrosine kinase inhibitors targeting the fusion products in fusion-positive LADCs. Structural analysis of breakpoint junctions of ALK, RET, and ROS1 fusions demonstrated that oncogene fusion is produced by illegitimate repair of DSBs at unspecified sites in genomic regions of a few kb through DNA synthesis-dependent or -independent end-joining pathways.

Free Research Field

がん遺伝学