Investigation of genetic alteration and molecular basis of de novo colorectal cancer

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860518
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Yokohama City University
• Principal Investigator: SAKAI Eiji 横浜市立大学, 医学(系)研究科(研究院), 客員研究員 (30600233)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 大腸癌 / 遺伝子変異

Outline of Final Research Achievements

In this study, we revealed molecular basis of laterally spreading tumor (LST), using genome-wide comprehensive analyses. Firstly, we assessed their epigenetic background. Subsequently, we conducted targeted exon sequencing including 38 candidate CRC driver genes. By hierarchical clustering using methylation information, LST was clearly classified into two subtypes; LST-G correlating to IME, and LST-NG correlating to LME. Genes associated with RTK/RAS signaling pathway were mutated more frequently in LST-G than LST-NG (P=0.004), especially KRAS mutation. Both LSTs showed high frequency of APC mutation even at adenoma stage, suggesting its involvement in initiation stage of LST, like adenoma-carcinoma sequence. TP53 mutation was specifically detected in cancer samples. TP53 mutation occurred during development of intramucosal cancer in LST-NG, but during development of cancer with submucosal invasion in LST-G, suggesting involvement of TP53 mutation at earlier stage in LST-NG.

Free Research Field

大腸癌