Targetable signaling pathway mutations are associated with malignant phenotype in IDH-mutant gliomas.
OBJECTIVE
Isocitrate dehydrogenase (IDH) gene mutations occur in low-grade and high-grade gliomas. We sought to identify the genetic basis of malignant phenotype heterogeneity in IDH-mutant gliomas.


METHODS
We prospectively implanted tumor specimens from 20 consecutive IDH1-mutant glioma resections into mouse brains and genotyped all resection specimens using a CLIA-certified molecular panel. Gliomas with cancer driver mutations were tested for sensitivity to targeted inhibitors in vitro. Associations between genomic alterations and outcomes were analyzed in patients.


RESULTS
By 10 months, 8 of 20 IDH1-mutant gliomas developed intracerebral xenografts. All xenografts maintained mutant IDH1 and high levels of 2-hydroxyglutarate on serial transplantation. All xenograft-producing gliomas harbored "lineage-defining" mutations in CIC (oligodendroglioma) or TP53 (astrocytoma), and 6 of 8 additionally had activating mutations in PIK3CA or amplification of PDGFRA, MET, or N-MYC. Only IDH1 and CIC/TP53 mutations were detected in non-xenograft-forming gliomas (P = 0.0007). Targeted inhibition of the additional alterations decreased proliferation in vitro. Moreover, we detected alterations in known cancer driver genes in 13.4% of IDH-mutant glioma patients, including PIK3CA, KRAS, AKT, or PTEN mutation or PDGFRA, MET, or N-MYC amplification. IDH/CIC mutant tumors were associated with PIK3CA/KRAS mutations whereas IDH/TP53 tumors correlated with PDGFRA/MET amplification. Presence of driver alterations at progression was associated with shorter subsequent progression-free survival (median 9.0 vs. 36.1 months; P = 0.0011).


CONCLUSIONS
A subset of IDH-mutant gliomas with mutations in driver oncogenes has a more malignant phenotype in patients. Identification of these alterations may provide an opportunity for use of targeted therapies in these patients. Clin Cancer Res; 20(11); 2898-909. ©2014 AACR.
Authors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, BelgiumAuthors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, BelgiumAuthors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, Belgium.
Hiroaki
H
Wakimoto
Authors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, BelgiumAuthors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, BelgiumAuthors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, Belgium.
Shota
S
Tanaka
Authors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, BelgiumAuthors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, Belgium.
William T
WT
Curry
Authors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, BelgiumAuthors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, BelgiumAuthors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, Belgium.
Franziska
F
Loebel
Authors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, BelgiumAuthors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, BelgiumAuthors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, Belgium.
Dan
D
Zhao
Authors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, BelgiumAuthors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, BelgiumAuthors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, Belgium.
Kensuke
K
Tateishi
Authors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, BelgiumAuthors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, BelgiumAuthors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, Belgium.
Juxiang
J
Chen
Authors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, BelgiumAuthors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, BelgiumAuthors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, Belgium.
Lindsay K
LK
Klofas
Authors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, BelgiumAuthors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, BelgiumAuthors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, Belgium.
Nina
N
Lelic
Authors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, BelgiumAuthors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, Belgium.
James C
JC
Kim
Authors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, BelgiumAuthors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, Belgium.
Dora
D
Dias-Santagata
Authors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, BelgiumAuthors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, Belgium.
Leif W
LW
Ellisen
Authors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, BelgiumAuthors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, Belgium.
Darrell R
DR
Borger
Authors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, Belgium.
Sarah-Maria
SM
Fendt
Authors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, Belgium.
Matthew G
MG
Vander Heiden
Authors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, BelgiumAuthors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, BelgiumAuthors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, Belgium.
Tracy T
TT
Batchelor
Authors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, BelgiumAuthors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, BelgiumAuthors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, Belgium.
A John
AJ
Iafrate
Authors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, BelgiumAuthors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, BelgiumAuthors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, Belgium.
Daniel P
DP
Cahill
Authors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, BelgiumAuthors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, BelgiumAuthors' Affiliations: Department of Neurosurgery; Division of Hematology/Oncology, Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Translational Research Laboratory; Department of Pathology; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; Translational Neuro-Oncology Laboratory; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; Vesalius Research Center, VIB and Department of Oncology, KU Leuven, Leuven, Belgium chi.andrew@mgh.harvard.edu cahill@mgh.harvard.edu.
Andrew S
AS
Chi
D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D018572:Disease-Free Survival; D008401:Gas Chromatography-Mass Spectrometry; D005910:Glioma / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D064593:Heterografts; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D051379:Mice; D009154:Mutation; D009857:Oncogenes; D010641:Phenotype
D007521:Isocitrate Dehydrogenase