epigenetic drug development based on hierarchy and plasticity of malignant brain tumors

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390341
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Nagoya University
• Principal Investigator: NATSUME Atsushi 名古屋大学, 医学(系)研究科(研究院), 准教授 (30362255)
• Co-Investigator(Kenkyū-buntansha): WAKABAYASHI Toshihiko 名古屋大学, 医学系研究科, 教授 (50220835)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 脳腫瘍

Outline of Final Research Achievements

Here, combining high-throughput sequencing data of 757 cases from two large cohorts of grade-II/III gliomas, we delineated the entire picture of genetic alterations and affected pathways in grade-II/III gliomas with sensitive detection of driver genes. Grade-II/III gliomas comprise three distinct subtypes characterized by discrete sets of mutations and distinct clinical behaviors. Mutations showed significant positive/negative correlations and chronological hierarchy as inferred from different allelic burdens among coexisting mutations, suggesting functional interplays between mutations that drive clonal selection. Extensive serial/multi-regional sampling analyses further supported this and also revealed high degrees of temporal/spatial heterogeneity generated during tumor expansion and relapse, which should be shaped by complex, but ordered processes of multiple clonal selections/evolutions.

Free Research Field

脳腫瘍学