Exome sequencing of human breast cancer tissues resistant to taxanes.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10469
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Nagoya City University
• Principal Investigator: Endo Yumi 名古屋市立大学, 大学院医学研究科, 講師 (20566228)
• Co-Investigator(Kenkyū-buntansha): 遠山 竜也 名古屋市立大学, 大学院医学研究科, 教授 (30315882) ; 近藤 直人 名古屋市立大学, 大学院医学研究科, 講師 (90529166) ; 吉本 信保 名古屋市立大学, 大学院医学研究科, 研究員 (10551244)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 乳癌 / 薬剤耐性 / 体細胞変異

Outline of Final Research Achievements

The aim of this study was to investigate the mechanisms of taxane resistance using whole exon sequencing and expression analyses in human breast cancer tissues.
We selected six breast cancer patients whose tumors responded well to anthracycline treatment but suffered disease progression on taxane treatment. We then performed whole exon sequencing on these samples . In this way, we identified somatic mutations of candidate genes considered to be instrumental for mediating resistance to taxanes. These candidate genes were APOBEC3F and ATP6V1A.　Kaplan-Meier analyses showed that high level mRNA expression of two genes were significantly associated with poorer disease-free survival (DFS) and overall survival (OS). However, there were no significant correlations between protein expression levels and DFS and OS. We conducted a search for these two mutations about 122 breast cancers treated with taxanes. Among these patients, no mutations were found about both ATP6V1A and APOBEC3F.

Free Research Field

乳癌の生物学的特性について

Academic Significance and Societal Importance of the Research Achievements

タキサン系薬剤抵抗性は、多くの癌種で問題となっている、さらに、ATP6V1AやAPOBEC3の遺伝子の異常は乳癌以外の癌でも多く観察されている。よって、本研究の実施により、いわゆる難治癌を含む多くの癌種に対する治療のブレークスルーになることが期待できるため、社会的な意義はきわめて大きい。