The somatic genomic landscape of glioblastoma

Cameron W. Brennan; Roel G.W. Verhaak; Aaron McKenna; Benito Campos; Houtan Noushmehr; Sofie R. Salama; Siyuan Zheng; Debyani Chakravarty; J. Zachary Sanborn; Samuel H. Berman; Rameen Beroukhim; Brady Bernard; Chang Jiun Wu; Giannicola Genovese; Ilya Shmulevich; Jill Barnholtz-Sloan; Lihua Zou; Rahulsimham Vegesna; Sachet A. Shukla; Giovanni Ciriello; W. K. Yung; Wei Zhang; Carrie Sougnez; Tom Mikkelsen; Kenneth Aldape; Darell D. Bigner; Erwin G. Van Meir; Michael Prados; Andrew Sloan; Keith L. Black; Jennifer Eschbacher; Gaetano Finocchiaro; William Friedman; David W. Andrews; Abhijit Guha; Mary Iacocca; Brian P. O'Neill; Greg Foltz; Jerome Myers; Daniel J. Weisenberger; Robert Penny; Raju Kucherlapati; Charles M. Perou; D. Neil Hayes; Richard Gibbs; Marco Marra; Gordon B. Mills; Eric Lander; Paul Spellman; Daniel Brat; TCGA Research Network

doi:10.1016/j.cell.2013.09.034

The somatic genomic landscape of glioblastoma

Cameron W. Brennan^*, Roel G.W. Verhaak, Aaron McKenna, Benito Campos, Houtan Noushmehr, Sofie R. Salama, Siyuan Zheng, Debyani Chakravarty, J. Zachary Sanborn, Samuel H. Berman, Rameen Beroukhim, Brady Bernard, Chang Jiun Wu, Giannicola Genovese, Ilya Shmulevich, Jill Barnholtz-Sloan, Lihua Zou, Rahulsimham Vegesna, Sachet A. Shukla, Giovanni CirielloW. K. Yung, Wei Zhang, Carrie Sougnez, Tom Mikkelsen, Kenneth Aldape, Darell D. Bigner, Erwin G. Van Meir, Michael Prados, Andrew Sloan, Keith L. Black, Jennifer Eschbacher, Gaetano Finocchiaro, William Friedman, David W. Andrews, Abhijit Guha, Mary Iacocca, Brian P. O'Neill, Greg Foltz, Jerome Myers, Daniel J. Weisenberger, Robert Penny, Raju Kucherlapati, Charles M. Perou, D. Neil Hayes, Richard Gibbs, Marco Marra, Gordon B. Mills, Eric Lander, Paul Spellman, Daniel Brat, TCGA Research Network

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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 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.

Original language	English (US)
Pages (from-to)	462
Number of pages	1
Journal	Cell
Volume	155
Issue number	2
DOIs	https://doi.org/10.1016/j.cell.2013.09.034
State	Published - Oct 10 2013

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cell.2013.09.034

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Brennan, C. W., Verhaak, R. G. W., McKenna, A., Campos, B., Noushmehr, H., Salama, S. R., Zheng, S., Chakravarty, D., Sanborn, J. Z., Berman, S. H., Beroukhim, R., Bernard, B., Wu, C. J., Genovese, G., Shmulevich, I., Barnholtz-Sloan, J., Zou, L., Vegesna, R., Shukla, S. A., ... TCGA Research Network (2013). The somatic genomic landscape of glioblastoma. Cell, 155(2), 462. https://doi.org/10.1016/j.cell.2013.09.034

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title = "The somatic genomic landscape of glioblastoma",

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 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.",

author = "Brennan, {Cameron W.} and Verhaak, {Roel G.W.} and Aaron McKenna and Benito Campos and Houtan Noushmehr and Salama, {Sofie R.} and Siyuan Zheng and Debyani Chakravarty and Sanborn, {J. Zachary} and Berman, {Samuel H.} and Rameen Beroukhim and Brady Bernard and Wu, {Chang Jiun} and Giannicola Genovese and Ilya Shmulevich and Jill Barnholtz-Sloan and Lihua Zou and Rahulsimham Vegesna and Shukla, {Sachet A.} and Giovanni Ciriello and Yung, {W. K.} and Wei Zhang and Carrie Sougnez and Tom Mikkelsen and Kenneth Aldape and Bigner, {Darell D.} and {Van Meir}, {Erwin G.} and Michael Prados and Andrew Sloan and Black, {Keith L.} and Jennifer Eschbacher and Gaetano Finocchiaro and William Friedman and Andrews, {David W.} and Abhijit Guha and Mary Iacocca and O'Neill, {Brian P.} and Greg Foltz and Jerome Myers and Weisenberger, {Daniel J.} and Robert Penny and Raju Kucherlapati and Perou, {Charles M.} and Hayes, {D. Neil} and Richard Gibbs and Marco Marra and Mills, {Gordon B.} and Eric Lander and Paul Spellman and Daniel Brat and {TCGA Research Network}",

note = "Funding Information: The TCGA research network contributed collectively to this study. Biospecimens were provided by the Tissue Source Sites and processed by the Biospecimen Core Resource. Data generation and analyses were performed by the Genome Sequencing Centers, Cancer Genome Characterization Centers, and Genome Data Analysis Centers. All data were released through the Data Coordinating Center. Project activities were coordinated by NCI and NHGRI Project Teams. This work was supported by the following grants from the USA National Institutes of Health: U24CA143883, U24CA143858, U24CA143840, U24CA143799, U24CA143835, U24CA143845, U24CA143882, U24CA143867, U24CA143866, U24CA143848, U24CA144025, U24CA143843, U54HG003067, U54HG003079, U54HG003273, U24CA126543, U24CA126544, U24CA126546, U24CA126551, U24CA126554, U24CA126561, U24CA126563, and U24CA143731. Publisher Copyright: {\textcopyright} 2013 Elsevier Inc.",

year = "2013",

month = oct,

day = "10",

doi = "10.1016/j.cell.2013.09.034",

language = "English (US)",

volume = "155",

pages = "462",

journal = "Cell",

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Brennan, CW, Verhaak, RGW, McKenna, A, Campos, B, Noushmehr, H, Salama, SR, Zheng, S, Chakravarty, D, Sanborn, JZ, Berman, SH, Beroukhim, R, Bernard, B, Wu, CJ, Genovese, G, Shmulevich, I, Barnholtz-Sloan, J, Zou, L, Vegesna, R, Shukla, SA, Ciriello, G, Yung, WK, Zhang, W, Sougnez, C, Mikkelsen, T, Aldape, K, Bigner, DD, Van Meir, EG, Prados, M, Sloan, A, Black, KL, Eschbacher, J, Finocchiaro, G, Friedman, W, Andrews, DW, Guha, A, Iacocca, M, O'Neill, BP, Foltz, G, Myers, J, Weisenberger, DJ, Penny, R, Kucherlapati, R, Perou, CM, Hayes, DN, Gibbs, R, Marra, M, Mills, GB, Lander, E, Spellman, P, Brat, D & TCGA Research Network 2013, 'The somatic genomic landscape of glioblastoma', Cell, vol. 155, no. 2, pp. 462. https://doi.org/10.1016/j.cell.2013.09.034

TY - JOUR

T1 - The somatic genomic landscape of glioblastoma

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.

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

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 - Brat, Daniel

AU - TCGA Research Network

N1 - Funding Information: The TCGA research network contributed collectively to this study. Biospecimens were provided by the Tissue Source Sites and processed by the Biospecimen Core Resource. Data generation and analyses were performed by the Genome Sequencing Centers, Cancer Genome Characterization Centers, and Genome Data Analysis Centers. All data were released through the Data Coordinating Center. Project activities were coordinated by NCI and NHGRI Project Teams. This work was supported by the following grants from the USA National Institutes of Health: U24CA143883, U24CA143858, U24CA143840, U24CA143799, U24CA143835, U24CA143845, U24CA143882, U24CA143867, U24CA143866, U24CA143848, U24CA144025, U24CA143843, U54HG003067, U54HG003079, U54HG003273, U24CA126543, U24CA126544, U24CA126546, U24CA126551, U24CA126554, U24CA126561, U24CA126563, and U24CA143731. 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.

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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 -

The somatic genomic landscape of glioblastoma

Abstract

ASJC Scopus subject areas

UN SDGs

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