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.
Description
Mutational landscape and clonal architecture in grade II and III gliomas. - PubMed - NCBI
%0 Journal Article
%1 Suzuki:2015:Nat-Genet:25848751
%A Suzuki, H
%A Aoki, K
%A Chiba, K
%A Sato, Y
%A Shiozawa, Y
%A Shiraishi, Y
%A Shimamura, T
%A Niida, A
%A Motomura, K
%A Ohka, F
%A Yamamoto, T
%A Tanahashi, K
%A Ranjit, M
%A Wakabayashi, T
%A Yoshizato, T
%A Kataoka, K
%A Yoshida, K
%A Nagata, Y
%A Sato-Otsubo, A
%A Tanaka, H
%A Sanada, M
%A Kondo, Y
%A Nakamura, H
%A Mizoguchi, M
%A Abe, T
%A Muragaki, Y
%A Watanabe, R
%A Ito, I
%A Miyano, S
%A Natsume, A
%A Ogawa, S
%D 2015
%J Nat Genet
%K PAYWALL cancer-research genomics glioma
%N 5
%P 458-468
%R 10.1038/ng.3273
%T Mutational landscape and clonal architecture in grade II and III gliomas
%U https://www.ncbi.nlm.nih.gov/pubmed/25848751?dopt=Abstract
%V 47
%X 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.
@article{Suzuki:2015:Nat-Genet:25848751,
abstract = {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.},
added-at = {2017-05-24T08:27:04.000+0200},
author = {Suzuki, H and Aoki, K and Chiba, K and Sato, Y and Shiozawa, Y and Shiraishi, Y and Shimamura, T and Niida, A and Motomura, K and Ohka, F and Yamamoto, T and Tanahashi, K and Ranjit, M and Wakabayashi, T and Yoshizato, T and Kataoka, K and Yoshida, K and Nagata, Y and Sato-Otsubo, A and Tanaka, H and Sanada, M and Kondo, Y and Nakamura, H and Mizoguchi, M and Abe, T and Muragaki, Y and Watanabe, R and Ito, I and Miyano, S and Natsume, A and Ogawa, S},
biburl = {https://www.bibsonomy.org/bibtex/27d4d6007cac33297d8d597044e2bda9c/marcsaric},
description = {Mutational landscape and clonal architecture in grade II and III gliomas. - PubMed - NCBI},
doi = {10.1038/ng.3273},
interhash = {124418ad6a9176ccbfc0577bb804070f},
intrahash = {7d4d6007cac33297d8d597044e2bda9c},
journal = {Nat Genet},
keywords = {PAYWALL cancer-research genomics glioma},
month = may,
number = 5,
pages = {458-468},
pmid = {25848751},
timestamp = {2017-05-24T08:27:04.000+0200},
title = {Mutational landscape and clonal architecture in grade II and III gliomas},
url = {https://www.ncbi.nlm.nih.gov/pubmed/25848751?dopt=Abstract},
volume = 47,
year = 2015
}