Multiregion analysis for early colorectal tumor

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19107
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: Kyushu University
• Principal Investigator: Saito Tomoko 九州大学, 大学病院, 医員 (10734741)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 早期大腸がん / 大腸線腫 / 全エキソームシーケンス / 腫瘍内不均一性 / 自然選択 / 枝分かれ進化

Outline of Final Research Achievements

Intratumor heterogeneity causes therapy resistance of cancer. Advanced colorectal cancer harbors extensive intratumor heterogeneity shaped by neutral evolution. We performed multiregion whole-exome sequencing on 10 early colorectal tumors, which contained adenoma and carcinoma in situ. By comparing with sequencing data from advanced colorectal tumors, we found that the early tumors accumulated a higher proportion of subclonal driver mutations than the advanced tumors. We also observed that variant allele frequencies of subclonal mutations tended to be higher in early tumors, suggesting that the subclonal mutations were subject to selective sweep in early tumorigenesis while neutral evolution is dominant in advanced ones. This study establishes that the evolutionary principle underlying intratumor heterogeneity shifts from Darwinian to neutral evolution during colorectal tumor progression.

Free Research Field

消化器内科