Clinicopathological analysis of RSPO fusion-positive colorectal carcinoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07382
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• 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): 2020-04-01 – 2023-03-31
• Keywords: 大腸癌 / WNT / R-spondin / RSPO / 鋸歯状病変

Outline of Final Research Achievements

We screened 1019 CRCs for RSPO fusions using multiplex reverse transcription-PCR, and subjected RSPO fusion-positive tumors to whole-exome sequencing (WES). Of the 1019 CRCs, 29 (2.8%) were found to harbor RSPO fusions, consisting of five with an EIF3E-RSPO2 fusion and 24 with PTPRK-RSPO3 fusions. Patients included 17 women and 12 men, and 13 tumors (45%) were right-sided. Half of the tumors (13/29, 45%) had a focal or extensive mucinous component, which was significantly more frequent than in RSPO fusion-negative tumors (13%; P = 8.1 × 10－7). WES identified KRAS, BRAF, and NRAS mutations in 27 tumors (93%). However, pathogenic mutations in major WNT pathway genes, such as APC, CTNNB1, and RNF43, were absent. Although RSPO fusion status did not significantly influence overall or recurrence-free survival. A pooled analysis of previous studies confirmed these clinicopathological and genetic features.

Free Research Field

人体病理学

Academic Significance and Societal Importance of the Research Achievements

R-spondin標的薬剤の臨床応用にあたっては、病理検体を用いてRSPO融合陽性例を同定し、適応となる患者を見つけ出す必要があるが、本研究によりRSPO融合陽性大腸癌の臨床病理学的・分子生物学的特徴が明らかになった。今後、効率的なRSPO融合の検出法の確立が期待される。