Comprehensive genomic characterization defines human glioblastoma genes and core pathways Journal Article

Author: The Cancer Genome Atlas Research Network
Contributors: Brennan, C.; Socci, N.; Olshen, A.; Taylor, B. S.; Lash, A.; Schultz, N.; Reva, B.; Antipin, Y.; Stukalov, A.; Gross, B.; Cerami, E.; Wang, W. Q.; Qin, L. X.; Seshan, V. E.; Villafania, L.; Cavatore, M.; Borsu, L.; Viale, A.; Gerald, W.; Sander, C.; Ladanyi, M.
Article Title: Comprehensive genomic characterization defines human glioblastoma genes and core pathways
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. ©2008 Macmillan Publishers Limited. All rights reserved.
Keywords: signal transduction; adolescent; adult; controlled study; human tissue; aged; aged, 80 and over; middle aged; retrospective studies; gene mutation; human cell; methylation; mutation; brain neoplasms; chromosome; dna repair; gene expression; cancer cell culture; enzyme activity; dna methylation; chromosome aberration; gene expression regulation, neoplastic; dna; brain; mismatch repair; glioblastoma; tumor suppressor proteins; 1-phosphatidylinositol 3-kinase; molecular analysis; dna repair enzymes; genomics; neurofibromin 1; genome; models, molecular; protein structure, tertiary; hominid; gene dosage; tumor; dna binding; dna modification methylases; dna determination; genes, tumor suppressor; genome, human; data set; genes, erbb-1
Journal Title: Nature
Volume: 455
Issue: 7216
ISSN: 0028-0836
Publisher: Nature Publishing Group  
Date Published: 2008-10-23
Start Page: 1061
End Page: 1068
Language: English
DOI: 10.1038/nature07385
PUBMED: 18772890
PROVIDER: scopus
PMCID: PMC2671642
Notes: Erratum/Corrigendum issued, see PMID: 23389443 and DOI: 10.1038/nature11903 -- "Cited By (since 1996): 831" - "Export Date: 17 November 2011" - "CODEN: NATUA" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Venkatraman Ennapadam Seshan
    285 Seshan
  2. Cameron Brennan
    151 Brennan
  3. William L Gerald
    367 Gerald
  4. Li-Xuan Qin
    114 Qin
  5. Marc Ladanyi
    863 Ladanyi
  6. Adam B Olshen
    107 Olshen
  7. Agnes Viale
    205 Viale
  8. Boris A Reva
    36 Reva
  9. Alex E Lash
    24 Lash
  10. Nicholas D Socci
    182 Socci
  11. Wei-Qing Wang
    9 Wang
  12. Chris Sander
    196 Sander
  13. Barry Stephen Taylor
    138 Taylor
  14. Ethan Cerami
    21 Cerami
  15. Nikolaus D Schultz
    196 Schultz
  16. Benjamin E Gross
    26 Gross
  17. Yevgeniy Antipin
    19 Antipin