Therapeutic option for ALK-positive lung cancer targeting the chromosomal translocation based on chromoslipsis

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10698
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: Chiba Cancer Center (Research Institute)
• Principal Investigator: Yokoi Sana 千葉県がんセンター(研究所), 遺伝子診断部, 部長 (30372452)
• Co-Investigator(Renkei-kenkyūsha): Iizasa Toshihiko
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 肺癌 / 染色体転座

Outline of Final Research Achievements

ALK inhibitors are effective for lung cancer with ALK translocation but become resistant within one year. In this study, genome-wide structural analysis of lung cancer with ALK translocation was performed, assuming that a reproducible genomic structural variation has occurred during the generation of chromosomal translocation on the chromosome 2 where ALK is located. As a result, we identified an ALK translocation-related gene that is located on the same chromosome 2 as ALK and causes reduced expression due to genomic deletion and promoter methylation. We also identified ALK translocation-related genes by bioinformatics analysis using an international cancer public database. These genes were considered to be potential therapeutic targets for lung cancer with ALK translocation.

Free Research Field

腫瘍遺伝学

Academic Significance and Societal Importance of the Research Achievements

癌の中でも特に難治性で悪性度が高いALK転座肺癌において、転座を起こしている二番染色体には特定のゲノム構造異常が生じていることを明らかにした。また、これら二番染色体上の欠失や構造異常が、ALK転座肺癌症例において特定の遺伝子の発現を変化させることを明らかにした。ALK転座の近傍に座位し、発現制御異常をきたし、癌化や悪性度に関わるこれらの遺伝子は、ALK転座肺癌の治療標的候補であると考えられた。