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Nature. 2008 Oct 23;455(7216):1061-8. doi: 10.1038/nature07385. Epub 2008 Sep 4.

Comprehensive genomic characterization defines human glioblastoma genes and core pathways.

Collaborators (231)

McLendon R, Friedman A, Bigner D, Van Meir EG, Brat DJ, Mastrogianakis GM, Olson JJ, Mikkelsen T, Lehman N, Aldape K, Yung WK, Bogler O, Weinstein JN, VandenBerg S, Berger M, Prados M, Muzny D, Morgan M, Scherer S, Sabo A, Nazareth L, Lewis L, Hall O, Zhu Y, Ren Y, Alvi O, Yao J, Hawes A, Jhangiani S, Fowler G, San Lucas A, Kovar C, Cree A, Dinh H, Santibanez J, Joshi V, Gonzalez-Garay ML, Miller CA, Milosavljevic A, Donehower L, Wheeler DA, Gibbs RA, Cibulskis K, Sougnez C, Fennell T, Mahan S, Wilkinson J, Ziaugra L, Onofrio R, Bloom T, Nicol R, Ardlie K, Baldwin J, Gabriel S, Lander ES, Ding L, Fulton RS, McLellan MD, Wallis J, Larson DE, Shi X, Abbott R, Fulton L, Chen K, Koboldt DC, Wendl MC, Meyer R, Tang Y, Lin L, Osborne JR, Dunford-Shore BH, Miner TL, Delehaunty K, Markovic C, Swift G, Courtney W, Pohl C, Abbott S, Hawkins A, Leong S, Haipek C, Schmidt H, Wiechert M, Vickery T, Scott S, Dooling DJ, Chinwalla A, Weinstock GM, Mardis ER, Wilson RK, Getz G, Winckler W, Verhaak RG, Lawrence MS, O'Kelly M, Robinson J, Alexe G, Beroukhim R, Carter S, Chiang D, Gould J, Gupta S, Korn J, Mermel C, Mesirov J, Monti S, Nguyen H, Parkin M, Reich M, Stransky N, Weir BA, Garraway L, Golub T, Meyerson M, Chin L, Protopopov A, Zhang J, Perna I, Aronson S, Sathiamoorthy N, Ren G, Yao J, Wiedemeyer WR, Kim H, Kong SW, Xiao Y, Kohane IS, Seidman J, Park PJ, Kucherlapati R, Laird PW, Cope L, Herman JG, Weisenberger DJ, Pan F, Van den Berg D, Van Neste L, Yi JM, Schuebel KE, Baylin SB, Absher DM, Li JZ, Southwick A, Brady S, Aggarwal A, Chung T, Sherlock G, Brooks JD, Myers RM, Spellman PT, Purdom E, Jakkula LR, Lapuk AV, Marr H, Dorton S, Choi YG, Han J, Ray A, Wang V, Durinck S, Robinson M, Wang NJ, Vranizan K, Peng V, Van Name E, Fontenay GV, Ngai J, Conboy JG, Parvin B, Feiler HS, Speed TP, Gray JW, Brennan C, Socci ND, Olshen A, Taylor BS, Lash A, Schultz N, Reva B, Antipin Y, Stukalov A, Gross B, Cerami E, Wang WQ, Qin LX, Seshan VE, Villafania L, Cavatore M, Borsu L, Viale A, Gerald W, Sander C, Ladanyi M, Perou CM, Hayes DN, Topal MD, Hoadley KA, Qi Y, Balu S, Shi Y, Wu J, Penny R, Bittner M, Shelton T, Lenkiewicz E, Morris S, Beasley D, Sanders S, Kahn A, Sfeir R, Chen J, Nassau D, Feng L, Hickey E, Barker A, Gerhard DS, Vockley J, Compton C, Vaught J, Fielding P, Ferguson ML, Schaefer C, Zhang J, Madhavan S, Buetow KH, Collins F, Good P, Guyer M, Ozenberger B, Peterson J, Thomson E.

Erratum in

  • Nature. 2013 Feb 28;494(7438):506.

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.

PMID:
18772890
[PubMed - indexed for MEDLINE]
PMCID:
PMC2671642
Free PMC Article

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