Analysis of the loss-of-function mechanism of mutant SETD2 and its application to immunotherapy for the patients with renal carcinoma

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K09550
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Osaka Medical and Pharmaceutical University
• Principal Investigator: Inamoto Teruo 大阪医科薬科大学, 医学部, 准教授 (20330087)
• Co-Investigator(Kenkyū-buntansha): 東 治人 大阪医科薬科大学, 医学部, 教授 (40231914)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 転移性腎癌 / 遺伝子変異 / 機能喪失

Outline of Final Research Achievements

Top genes that cause gene mutations at a frequency of 10% or more (VHL; 71.40%, PBRM1; 57.10%, SETD2; 42.90%, KDM5C; 20.00%, TTN; 17.10%, CACNA1I; 17.10%, BAP1; 14.30%, We comprehensively analyzed the ccRCC database of 1744 people (1813 samples) regarding DYNC1I1; 11.40%, MTOR; 11.40%) to assess the impact of genetic variants on the survival of ccRCC patients. SETD2 had the highest impact on patient survival among somatic mutations in renal cancer.

Free Research Field

泌尿器悪性腫瘍

Academic Significance and Societal Importance of the Research Achievements

いずれの腎癌免疫療法も効果が限定的である理由と解決のヒントは不明である。有力な原因遺伝子を同定し、将来、治療感受性を向上できるのであろうか。腎癌の分子病態の全容解析からすでに重要性が判明しているSETD2の免疫療法における役割の解析は直ちに取り組まないといけないもので、その結果は社会に還元できるものと考える。