TY - JOUR
T1 - The somatic genomic landscape of glioblastoma
AU - TCGA Research Network
AU - Brennan, Cameron W.
AU - Verhaak, Roel G.W.
AU - McKenna, Aaron
AU - Campos, Benito
AU - Noushmehr, Houtan
AU - Salama, Sofie R.
AU - Zheng, Siyuan
AU - Chakravarty, Debyani
AU - Sanborn, J. Zachary
AU - Berman, Samuel H.
AU - Beroukhim, Rameen
AU - Bernard, Brady
AU - Wu, Chang Jiun
AU - Genovese, Giannicola
AU - Shmulevich, Ilya
AU - Barnholtz-Sloan, Jill
AU - Zou, Lihua
AU - Vegesna, Rahulsimham
AU - Shukla, Sachet A.
AU - Ciriello, Giovanni
AU - Yung, W. K.Alfred
AU - Zhang, Wei
AU - Sougnez, Carrie
AU - Mikkelsen, Tom
AU - Aldape, Kenneth
AU - Bigner, Darell D.
AU - Van Meir, Erwin G.
AU - Prados, Michael
AU - Sloan, Andrew Edward
AU - Black, Keith L.
AU - Eschbacher, Jennifer
AU - Finocchiaro, Gaetano
AU - Friedman, William
AU - Andrews, David W.
AU - Guha, Abhijit
AU - Iacocca, Mary
AU - O'Neill, Brian P.
AU - Foltz, Greg
AU - Myers, Jerome
AU - Weisenberger, Daniel J.
AU - Penny, Robert
AU - Kucherlapati, Raju
AU - Perou, Charles M.
AU - Hayes, D. Neil
AU - Gibbs, Richard
AU - Marra, Marco
AU - Mills, Gordon B.
AU - Lander, Eric
AU - Spellman, Paul
AU - Baylin, Stephen B.
N1 - Publisher Copyright:
© 2013 Elsevier Inc.
PY - 2013/10/10
Y1 - 2013/10/10
N2 - We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations areshown tocorrelate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer.
AB - We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations areshown tocorrelate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer.
UR - http://www.scopus.com/inward/record.url?scp=84885074034&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84885074034&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2013.09.034
DO - 10.1016/j.cell.2013.09.034
M3 - Article
C2 - 24120142
AN - SCOPUS:84885074034
SN - 0092-8674
VL - 155
SP - 462
JO - Cell
JF - Cell
IS - 2
ER -