Publication

The Somatic Genomic Landscape of Glioblastoma.

Cell. 2013 Oct 10;155(2):462-477. doi: 10.1016/j.cell.2013.09.034.

Abstract

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 are shown to correlate 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.

Authors

Benz C, Barnholtz-Sloan J, Barrett W, Ostrom Q, Wolinsky Y, Black KL, Bose B, Boulos PT, Boulos M, Brown J, Czerinski C, Eppley M, Iacocca M, Kempista T, Kitko T, Koyfman Y, Rabeno B, Rastogi P, Sugarman M, Swanson P, Yalamanchii K, Otey IP, Liu YS, Xiao Y, Auman JT, Chen PC, Hadjipanayis A, Lee E, Lee S, Park PJ, Seidman J, Yang L, Kucherlapati R, Kalkanis S, Mikkelsen T, Poisson LM, Raghunathan A, Scarpace L, Bernard B, Bressler R, Eakin A, Iype L, Kreisberg RB, Leinonen K, Reynolds S, Rovira H, Thorsson V, Shmulevich I, Annala MJ, Penny R, Paulauskis J, Curley E, Hatfield M, Mallery D, Morris S, Shelton T, Shelton C, Sherman M, Yena P, Cuppini L, Dimeco F, Eoli M, Finocchiaro G, Maderna E, Pollo B, Saini M, Balu S, Hoadley KA, Li L, Miller CR, Shi Y, Topal MD, Wu J, Dunn G, Giannini C, O'Neill BP, Aksoy BA, Antipin Y, Borsu L, Berman SH, Brennan CW, Cerami E, Chakravarty D, Ciriello G, Gao J, Gross B, Jacobsen A, Ladanyi M, Lash A, Liang Y, Reva B, Sander C, Schultz N, Shen R, Socci ND, Viale A, Ferguson ML, Chen QR, Demchok JA, Dillon LA, Shaw KR, Sheth M, Tarnuzzer R, Wang Z, Yang L, Davidsen T, Guyer MS, Ozenberger BA, Sofia HJ, Bergsten J, Eckman J, Harr J, Myers J, Smith C, Tucker K, Winemiller C, Zach LA, Ljubimova JY, Eley G, Ayala B, Jensen MA, Kahn A, Pihl TD, Pot DA, Wan Y, Eschbacher J, Foltz G, Hansen N, Hothi P, Lin B, Shah N, Yoon JG, Lau C, Berens M, Ardlie K, Beroukhim R, Carter SL, Cherniack AD, Noble M, Cho J, Cibulskis K, Dicara D, Frazer S, Gabriel SB, Gehlenborg N, Gentry J, Heiman D, Kim J, Jing R, Lander ES, Lawrence M, Lin P, Mallard W, Meyerson M, Onofrio RC, Saksena G, Schumacher S, Sougnez C, Stojanov P, Tabak B, Voet D, Zhang H, Zou L, Getz G, Dees NN, Ding L, Fulton LL, Fulton RS, Kanchi KL, Mardis ER, Wilson RK, Baylin SB, Andrews DW, Harshyne L, Cohen ML, Devine K, Sloan AE, Vandenberg SR, Berger MS, Prados M, Carlin D, Craft B, Ellrott K, Goldman M, Goldstein T, Grifford M, Haussler D, Ma S, Ng S, Salama SR, Sanborn JZ, Stuart J, Swatloski T, Waltman P, Zhu J, Foss R, Frentzen B, Friedman W, McTiernan R, Yachnis A, Hayes DN, Perou CM, Zheng S, Vegesna R, Mao Y, Akbani R, Aldape K, Bogler O, Fuller GN, Liu W, Liu Y, Lu Y, Mills G, Protopopov A, Ren X, Sun Y, Wu CJ, Yung WK, Zhang W, Zhang J, Chen K, Weinstein JN, Chin L, Verhaak RG, Noushmehr H, Weisenberger DJ, Bootwalla MS, Lai PH, Triche TJ Jr, Van Den Berg DJ, Laird PW, Gutmann DH, Lehman NL, Vanmeir EG, Brat D, Olson JJ, Mastrogianakis GM, Devi NS, Zhang Z, Bigner D, Lipp E, McLendon R.