Novel treatment strategy for colorectal cancer based on genetic/ epigenetic information

2015 Fiscal Year Final Research Report

• Project/Area Number: 25860409
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory medicine
• Research Institution: Okayama University
• Principal Investigator: Umeda Yuzo 岡山大学, 大学病院, 助教 (10573735)
• Co-Investigator(Renkei-kenkyūsha): FUJIWARA Toshiyoshi 岡山大学, 医歯薬学総合研究科 消化器外科, 教授 (00304303) ; YAGI Takahito 岡山大学, 大学病院 肝胆膵外科, 教授 (00304353) ; NAGASAKA Takeshi 岡山大学, 大学病院 消化器外科, 講師 (30452569)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 大腸癌 / 大腸癌肝転移 / 遺伝子解析

Outline of Final Research Achievements

We previously reported that genetic information has an essential role as a prognostic/predictive marker in treatment strategy for colorectal cancer (CRC).
The aim of the research was to discover novel epigenetic biomarkers. BRAF V600E was initially focused on because microsatellite stable (MSS) CRC with BRAF V600E mutation(mt) fails to extremely poor outcome. We analyzed 17-gene methylation panel that consists of different methylation loci in BRAF V600E with MSS and microsatellite instability (MSI). This analysis identified demethylation of O6-methylguanine DNA methyltransferase (MGMT). BRAF V600E-mt with MSS didn’t show MGMT methylation, while that with MSI showed partial or extensive methylation of MGMT promoter. And this could be observed in KRAS-mt and wild type CRC. In utilization to the patient cohort of stage II/III CRC (n=223), MGMT hyper methylation associated with improved relapse-free survival.
In conclusion, MGMT methylation status could be a promising biomarker of CRC.

Free Research Field

消化器外科