Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1

Roel G W Verhaak; Katherine A. Hoadley; Elizabeth Purdom; Victoria Wang; Yuan Qi; Matthew D. Wilkerson; C. Ryan Miller; Li Ding; Todd Golub; Jill P. Mesirov; Gabriele Alexe; Michael Lawrence; Michael O'Kelly; Pablo Tamayo; Barbara A. Weir; Stacey Gabriel; Wendy Winckler; Supriya Gupta; Lakshmi Jakkula; Heidi S. Feiler; J. Graeme Hodgson; C. David James; Jann N. Sarkaria; Cameron Brennan; Ari Kahn; Paul T. Spellman; Richard K. Wilson; Terence P. Speed; Joe W. Gray; Matthew Meyerson; Gad Getz; Charles M. Perou; D. Neil Hayes

doi:10.1016/j.ccr.2009.12.020

Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1

Roel G W Verhaak, Katherine A. Hoadley, Elizabeth Purdom, Victoria Wang, Yuan Qi, Matthew D. Wilkerson, C. Ryan Miller, Li Ding, Todd Golub, Jill P. Mesirov, Gabriele Alexe, Michael Lawrence, Michael O'Kelly, Pablo Tamayo, Barbara A. Weir, Stacey Gabriel, Wendy Winckler, Supriya Gupta, Lakshmi Jakkula, Heidi S. FeilerJ. Graeme Hodgson, C. David James, Jann N. Sarkaria, Cameron Brennan, Ari Kahn, Paul T. Spellman, Richard K. Wilson, Terence P. Speed, Joe W. Gray, Matthew Meyerson, Gad Getz, Charles M. Perou, D. Neil Hayes^*

^*Corresponding author for this work

Neurological Surgery

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

5761 Scopus citations

Abstract

The Cancer Genome Atlas Network recently cataloged recurrent genomic abnormalities in glioblastoma multiforme (GBM). We describe a robust gene expression-based molecular classification of GBM into Proneural, Neural, Classical, and Mesenchymal subtypes and integrate multidimensional genomic data to establish patterns of somatic mutations and DNA copy number. Aberrations and gene expression of EGFR, NF1, and PDGFRA/IDH1 each define the Classical, Mesenchymal, and Proneural subtypes, respectively. Gene signatures of normal brain cell types show a strong relationship between subtypes and different neural lineages. Additionally, response to aggressive therapy differs by subtype, with the greatest benefit in the Classical subtype and no benefit in the Proneural subtype. We provide a framework that unifies transcriptomic and genomic dimensions for GBM molecular stratification with important implications for future studies.

Original language	English (US)
Pages (from-to)	98-110
Number of pages	13
Journal	Cancer cell
Volume	17
Issue number	1
DOIs	https://doi.org/10.1016/j.ccr.2009.12.020
State	Published - Jan 19 2010

Funding

We thank the members of TCGA Research Network, in particular Lynda Chin, for reviewing this manuscript. We thank Michele Hayward for editorial assistance. This work was supported by the following grants from the US Department of Energy and the US National Institutes of Health: U54HG003067 and U54HG003079 to R.K.W.; U54HG003273, U24CA126543, and U24CA126544 to C.M.P.; U24CA126546 to M.M.; U24CA126551 to J.W.G.; U24CA126554, U24CA126561, U24CA126563, and P50CA58223 to C.M.P.; RR023248 to D.N.H.; CA108961 to J.N.S.; CA127716 to J.N.S.; NS49720 to C.D.J.; CA097257 to C.D.J.; and DE-AC02-05CH11231 to J.W.G.). R.G.W.V. is supported by a Fellowship from the Dutch Cancer Society KWF.

Keywords

CELLCYCLE

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

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

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10.1016/j.ccr.2009.12.020

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Verhaak, R. G. W., Hoadley, K. A., Purdom, E., Wang, V., Qi, Y., Wilkerson, M. D., Miller, C. R., Ding, L., Golub, T., Mesirov, J. P., Alexe, G., Lawrence, M., O'Kelly, M., Tamayo, P., Weir, B. A., Gabriel, S., Winckler, W., Gupta, S., Jakkula, L., ... Hayes, D. N. (2010). Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer cell, 17(1), 98-110. https://doi.org/10.1016/j.ccr.2009.12.020

@article{50ed1f404e0f4a70b650deeed8cc63e9,

title = "Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1",

abstract = "The Cancer Genome Atlas Network recently cataloged recurrent genomic abnormalities in glioblastoma multiforme (GBM). We describe a robust gene expression-based molecular classification of GBM into Proneural, Neural, Classical, and Mesenchymal subtypes and integrate multidimensional genomic data to establish patterns of somatic mutations and DNA copy number. Aberrations and gene expression of EGFR, NF1, and PDGFRA/IDH1 each define the Classical, Mesenchymal, and Proneural subtypes, respectively. Gene signatures of normal brain cell types show a strong relationship between subtypes and different neural lineages. Additionally, response to aggressive therapy differs by subtype, with the greatest benefit in the Classical subtype and no benefit in the Proneural subtype. We provide a framework that unifies transcriptomic and genomic dimensions for GBM molecular stratification with important implications for future studies.",

keywords = "CELLCYCLE",

author = "Verhaak, {Roel G W} and Hoadley, {Katherine A.} and Elizabeth Purdom and Victoria Wang and Yuan Qi and Wilkerson, {Matthew D.} and Miller, {C. Ryan} and Li Ding and Todd Golub and Mesirov, {Jill P.} and Gabriele Alexe and Michael Lawrence and Michael O'Kelly and Pablo Tamayo and Weir, {Barbara A.} and Stacey Gabriel and Wendy Winckler and Supriya Gupta and Lakshmi Jakkula and Feiler, {Heidi S.} and Hodgson, {J. Graeme} and James, {C. David} and Sarkaria, {Jann N.} and Cameron Brennan and Ari Kahn and Spellman, {Paul T.} and Wilson, {Richard K.} and Speed, {Terence P.} and Gray, {Joe W.} and Matthew Meyerson and Gad Getz and Perou, {Charles M.} and Hayes, {D. Neil}",

note = "Funding Information: We thank the members of TCGA Research Network, in particular Lynda Chin, for reviewing this manuscript. We thank Michele Hayward for editorial assistance. This work was supported by the following grants from the US Department of Energy and the US National Institutes of Health: U54HG003067 and U54HG003079 to R.K.W.; U54HG003273, U24CA126543, and U24CA126544 to C.M.P.; U24CA126546 to M.M.; U24CA126551 to J.W.G.; U24CA126554, U24CA126561, U24CA126563, and P50CA58223 to C.M.P.; RR023248 to D.N.H.; CA108961 to J.N.S.; CA127716 to J.N.S.; NS49720 to C.D.J.; CA097257 to C.D.J.; and DE-AC02-05CH11231 to J.W.G.). R.G.W.V. is supported by a Fellowship from the Dutch Cancer Society KWF. ",

year = "2010",

month = jan,

day = "19",

doi = "10.1016/j.ccr.2009.12.020",

language = "English (US)",

volume = "17",

pages = "98--110",

journal = "Cancer cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "1",

}

Verhaak, RGW, Hoadley, KA, Purdom, E, Wang, V, Qi, Y, Wilkerson, MD, Miller, CR, Ding, L, Golub, T, Mesirov, JP, Alexe, G, Lawrence, M, O'Kelly, M, Tamayo, P, Weir, BA, Gabriel, S, Winckler, W, Gupta, S, Jakkula, L, Feiler, HS, Hodgson, JG, James, CD, Sarkaria, JN, Brennan, C, Kahn, A, Spellman, PT, Wilson, RK, Speed, TP, Gray, JW, Meyerson, M, Getz, G, Perou, CM & Hayes, DN 2010, 'Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1', Cancer cell, vol. 17, no. 1, pp. 98-110. https://doi.org/10.1016/j.ccr.2009.12.020

TY - JOUR

T1 - Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1

AU - Verhaak, Roel G W

AU - Hoadley, Katherine A.

AU - Purdom, Elizabeth

AU - Wang, Victoria

AU - Qi, Yuan

AU - Wilkerson, Matthew D.

AU - Miller, C. Ryan

AU - Ding, Li

AU - Golub, Todd

AU - Mesirov, Jill P.

AU - Alexe, Gabriele

AU - Lawrence, Michael

AU - O'Kelly, Michael

AU - Tamayo, Pablo

AU - Weir, Barbara A.

AU - Gabriel, Stacey

AU - Winckler, Wendy

AU - Gupta, Supriya

AU - Jakkula, Lakshmi

AU - Feiler, Heidi S.

AU - Hodgson, J. Graeme

AU - James, C. David

AU - Sarkaria, Jann N.

AU - Brennan, Cameron

AU - Kahn, Ari

AU - Spellman, Paul T.

AU - Wilson, Richard K.

AU - Speed, Terence P.

AU - Gray, Joe W.

AU - Meyerson, Matthew

AU - Getz, Gad

AU - Perou, Charles M.

AU - Hayes, D. Neil

N1 - Funding Information: We thank the members of TCGA Research Network, in particular Lynda Chin, for reviewing this manuscript. We thank Michele Hayward for editorial assistance. This work was supported by the following grants from the US Department of Energy and the US National Institutes of Health: U54HG003067 and U54HG003079 to R.K.W.; U54HG003273, U24CA126543, and U24CA126544 to C.M.P.; U24CA126546 to M.M.; U24CA126551 to J.W.G.; U24CA126554, U24CA126561, U24CA126563, and P50CA58223 to C.M.P.; RR023248 to D.N.H.; CA108961 to J.N.S.; CA127716 to J.N.S.; NS49720 to C.D.J.; CA097257 to C.D.J.; and DE-AC02-05CH11231 to J.W.G.). R.G.W.V. is supported by a Fellowship from the Dutch Cancer Society KWF.

PY - 2010/1/19

Y1 - 2010/1/19

N2 - The Cancer Genome Atlas Network recently cataloged recurrent genomic abnormalities in glioblastoma multiforme (GBM). We describe a robust gene expression-based molecular classification of GBM into Proneural, Neural, Classical, and Mesenchymal subtypes and integrate multidimensional genomic data to establish patterns of somatic mutations and DNA copy number. Aberrations and gene expression of EGFR, NF1, and PDGFRA/IDH1 each define the Classical, Mesenchymal, and Proneural subtypes, respectively. Gene signatures of normal brain cell types show a strong relationship between subtypes and different neural lineages. Additionally, response to aggressive therapy differs by subtype, with the greatest benefit in the Classical subtype and no benefit in the Proneural subtype. We provide a framework that unifies transcriptomic and genomic dimensions for GBM molecular stratification with important implications for future studies.

AB - The Cancer Genome Atlas Network recently cataloged recurrent genomic abnormalities in glioblastoma multiforme (GBM). We describe a robust gene expression-based molecular classification of GBM into Proneural, Neural, Classical, and Mesenchymal subtypes and integrate multidimensional genomic data to establish patterns of somatic mutations and DNA copy number. Aberrations and gene expression of EGFR, NF1, and PDGFRA/IDH1 each define the Classical, Mesenchymal, and Proneural subtypes, respectively. Gene signatures of normal brain cell types show a strong relationship between subtypes and different neural lineages. Additionally, response to aggressive therapy differs by subtype, with the greatest benefit in the Classical subtype and no benefit in the Proneural subtype. We provide a framework that unifies transcriptomic and genomic dimensions for GBM molecular stratification with important implications for future studies.

KW - CELLCYCLE

UR - http://www.scopus.com/inward/record.url?scp=73649123907&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=73649123907&partnerID=8YFLogxK

U2 - 10.1016/j.ccr.2009.12.020

DO - 10.1016/j.ccr.2009.12.020

M3 - Article

C2 - 20129251

AN - SCOPUS:73649123907

SN - 1535-6108

VL - 17

SP - 98

EP - 110

JO - Cancer cell

JF - Cancer cell

IS - 1

ER -

Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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