Two subtypes of colorectal tumor with distinct molecular features in familial adenoma polyposis

2016 Fiscal Year Final Research Report

• Project/Area Number: 15H06098
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Digestive surgery
• Research Institution: Chiba University
• Principal Investigator: Takane Kiyoko 千葉大学, 大学院医学研究院, 特任助教 (60756112)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Keywords: 家族性大腸線腫症 / 大腸癌 / 大腸線腫症 / DNAメチル化

Outline of Final Research Achievements

Familial adenomatous polyposis (FAP) tumors is yet to be well investigated. Here, we investigated FAP, through quantitative methylation analysis of 127 samples using 20 methylation markers we previously established, APC, BRAF, and KRAS mutation analysis. FAP tumors lacked BRAF mutation(+) high methylation epigenotype and were classified into two methylation epigenotypes. While 24 of 112 tumor samples showed intermediate methylation epigenotype significantly correlating with KRAS mutation(+), 88 tumor samples showed low methylation epigenotype correlating with the absence of KRAS and BRAF mutations. Whereas some patients showed a single epigenotype in all tumors throughout the colon, tumors with two distinct epigenotypes developed within a family with the same APC mutation or even within one patient. These results indicate that there are at least two distinct molecular subtypes of FAP tumors, resembling sporadic colorectal cancer and independent from the APC germline mutation status.

Free Research Field

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