Mutational landscape and clonal architecture in grade II and III gliomas.

Published

Journal Article

Grade II and III gliomas are generally slowly progressing brain cancers, many of which eventually transform into more aggressive tumors. Despite recent findings of frequent mutations in IDH1 and other genes, knowledge about their pathogenesis is still incomplete. Here, combining two large sets of high-throughput sequencing data, we delineate the entire picture of genetic alterations and affected pathways in these glioma types, with sensitive detection of driver genes. Grade II and III gliomas comprise three distinct subtypes characterized by discrete sets of mutations and distinct clinical behaviors. Mutations showed significant positive and negative correlations and a chronological hierarchy, as inferred from different allelic burdens among coexisting mutations, suggesting that there is functional interplay between the mutations that drive clonal selection. Extensive serial and multi-regional sampling analyses further supported this finding and also identified a high degree of temporal and spatial heterogeneity generated during tumor expansion and relapse, which is likely shaped by the complex but ordered processes of multiple clonal selection and evolutionary events.

Full Text

Cited Authors

  • Suzuki, H; Aoki, K; Chiba, K; Sato, Y; Shiozawa, Y; Shiraishi, Y; Shimamura, T; Niida, A; Motomura, K; Ohka, F; Yamamoto, T; Tanahashi, K; Ranjit, M; Wakabayashi, T; Yoshizato, T; Kataoka, K; Yoshida, K; Nagata, Y; Sato-Otsubo, A; Tanaka, H; Sanada, M; Kondo, Y; Nakamura, H; Mizoguchi, M; Abe, T; Muragaki, Y; Watanabe, R; Ito, I; Miyano, S; Natsume, A; Ogawa, S

Published Date

  • May 2015

Published In

Volume / Issue

  • 47 / 5

Start / End Page

  • 458 - 468

PubMed ID

  • 25848751

Pubmed Central ID

  • 25848751

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

International Standard Serial Number (ISSN)

  • 1061-4036

Digital Object Identifier (DOI)

  • 10.1038/ng.3273

Language

  • eng