Molecular differences in the microsatellite stable phenotype between left-sided and right-sided colorectal cancer

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08700
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Iwate Medical University
• Principal Investigator: SUGAI TAMOTSU 岩手医科大学, 医学部, 教授 (20187628)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 大腸癌 / 左右差 / 発生部位 / コピー数異常 / TP53変異 / KRAS変異

Outline of Final Research Achievements

To identify genomic differences between MSS type left-sided CRC (LC) and right-sided CRC (RC), we examined a comprehensive molecular analysis using crypt isolation with samples from 92 sporadic CRCs. Microsatellite instability and DNA methylation status were determined. Additionally, mutations in the TP53, KRAS, BRAF, and PIK3CA genes were examined. Finally, a genome-wide study using a single nucleotide polymorphism array was performed. We examined 71 CRCs with the MSS phenotype (LC 56; RC, 15) in the 92 CRCs. Mutations in KRAS were associated with RC with the MSS phenotype, whereas mutations in TP53 were more frequently found in LC with the MSS phenotype. There were significant differences in the frequencies of KRAS and TP53 mutations between LC and RC with the MSS phenotype. CNA gains were associated with LC with the MSS phenotype. These findings suggested that the molecular pathogenesis of the MSS phenotype in LC was different from that in RC.

Free Research Field

人体病理学、分子病理学、腫瘍病理学、分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

大腸癌の発生機序が発生部位によって異なっているという指摘はこれまでなされていたが、それは右側にMSIを引き起こす癌が多いことを指摘している報告が多かった。大腸癌の分子病型では右側発生であってもMSS型が多く、MSS型癌の発生部位に基づいた分子レベルの違いを明らかにした報告は皆無である。本研究では発生部位に基づいたMSS型癌の特徴が明らかになった。近年右側発生の大腸癌の頻度が上昇する傾向があり、発生部位に基づいた大腸癌の分子機序を明らかにすることは大腸癌診療においても欠かすことのできない知見を提供するものと思われる。