Analysis of WNT pathway gene alteration in colorectal serrated lesions

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15109
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: National Cancer Center Japan
• Principal Investigator: Hashimoto Taiki 国立研究開発法人国立がん研究センター, 中央病院, 医員 (40773875)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 大腸癌 / 鋸歯状病変 / WNT

Outline of Final Research Achievements

We analyzed precursor polyp-associated TSAs by laser microdissection-based sequencing analysis and RNA in situ hybridization. Our analysis showed that BRAF or KRAS mutations were always shared between TSA and precursor components. However, WNT pathway gene alterations were restricted to the TSA component in most lesions.
We analyzed 99 TSAs and identified three lesions with EIF3E-RSPO2 fusion, which is a known recurrent RSPO fusion in colorectal cancer, and one with novel PIEZO1-RSPO2 fusion.

Free Research Field

大腸鋸歯状病変

Academic Significance and Societal Importance of the Research Achievements

本研究は、大腸癌の前駆病変と考えられている鋸歯状病変について、分子病理学的解析を行ったものである。本研究の結果、鋸歯状病変の形態変化と遺伝子異常の関係性が明らかになり大腸癌の発生メカニズムの理解が深まった。本成果は大腸癌に対する治療選択や前癌病変に対する適切なサーベイランスの立案に貢献するものと考えられる。