Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Academic Article uri icon

Overview

MeSH

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • DNA Methylation
  • DNA Modification Methylases
  • DNA Repair
  • DNA Repair Enzymes
  • Female
  • Gene Dosage
  • Genes, Tumor Suppressor
  • Genes, erbB-1
  • Genome, Human
  • Humans
  • Male
  • Middle Aged
  • Models, Molecular
  • Mutation
  • Neurofibromin 1
  • Phosphatidylinositol 3-Kinases
  • Protein Structure, Tertiary
  • Retrospective Studies
  • Signal Transduction
  • Tumor Suppressor Proteins

MeSH Major

  • Brain Neoplasms
  • Gene Expression Regulation, Neoplastic
  • Genomics
  • Glioblastoma

abstract

  • Human cancer cells typically harbour multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas (TCGA) pilot project aims to assess the value of large-scale multi-dimensional analysis of these molecular characteristics in human cancer and to provide the data rapidly to the research community. Here we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas--the most common type of adult brain cancer--and nucleotide sequence aberrations in 91 of the 206 glioblastomas. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the phosphatidylinositol-3-OH kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of glioblastoma. Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications. Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.

authors

publication date

  • October 23, 2008

has subject area

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Neoplasms
  • DNA Methylation
  • DNA Modification Methylases
  • DNA Repair
  • DNA Repair Enzymes
  • Female
  • Gene Dosage
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Genes, erbB-1
  • Genome, Human
  • Genomics
  • Glioblastoma
  • Humans
  • Male
  • Middle Aged
  • Models, Molecular
  • Mutation
  • Neurofibromin 1
  • Phosphatidylinositol 3-Kinases
  • Protein Structure, Tertiary
  • Retrospective Studies
  • Signal Transduction
  • Tumor Suppressor Proteins

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2671642

Digital Object Identifier (DOI)

  • 10.1038/nature07385

PubMed ID

  • 18772890

Additional Document Info

start page

  • 1061

end page

  • 1068

volume

  • 455

number

  • 7216