Molecular genetic analysis of adult high-grade gliomas, focusing on two subtypes

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06929
• 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: Kyorin University
• Principal Investigator: Shibahara Junji 杏林大学, 医学部, 教授 (60334380)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 膠腫 / 融合遺伝子 / FGFR3 / 多形性 / DNAメチル化

Outline of Final Research Achievements

DNA methylation profiling analyses of high-grade infiltrating gliomas harboring FGFR3::TACC3 fusion gene (F3T3-HGG), utilizing both in-house and public datasets, revealed that a subset of the cases exhibit a distinct DNA methylation profile. Additionally, it was shown that detecting increased FGFR3/TACC3 gene copy numbers enabled the diagnosis of F3T3-HGG with a reasonable accuracy.
Clinicopathological and molecular analyses were carried out on a newly defined tumor type termed polymorphic glioblastoma. The study revealed that polymorphic glioblastoma comprises a heterogeneous tumor group, including cases distinguished from conventional glioblastoma by features such as prolonged survival, loss of mismatch repair protein expression, or distinct DNA methylation profiles recently reported.

Free Research Field

人体病理学

Academic Significance and Societal Importance of the Research Achievements

FGFR3::TACC3融合遺伝子を有する高悪性度浸潤性膠腫の少なくとも一部が独特のDNAメチル化プロファイルを示すことは、本腫瘍の位置付けを決する上で有意義な知見である。分子標的薬の適応の点でも注目される本腫瘍のスクリーニング法は確立されておらず、遺伝子コピー数の検出により一定の精度で診断が可能であるを見出したことは、臨床的意義があると考えられる。多形型膠芽腫が膠芽腫としては非典型的な臨床病理学的・分子遺伝学的特徴を示す症例を高率に含むことを明らかにしたことは、膠芽腫の個別化医療の推進に重要な知見であると考えられる。