Molecular characterization of long-term survivors of glioblastoma using genome- and transcriptome-wide profiling
Standard
Molecular characterization of long-term survivors of glioblastoma using genome- and transcriptome-wide profiling. / Reifenberger, Guido; Weber, Ruthild G; Riehmer, Vera; Kaulich, Kerstin; Willscher, Edith; Wirth, Henry; Gietzelt, Jens; Hentschel, Bettina; Westphal, Manfred; Simon, Matthias; Schackert, Gabriele; Schramm, Johannes; Matschke, Jakob; Sabel, Michael C; Gramatzki, Dorothee; Felsberg, Jörg; Hartmann, Christian; Steinbach, Joachim P; Schlegel, Uwe; Wick, Wolfgang; Radlwimmer, Bernhard; Pietsch, Torsten; Tonn, Jörg C; von Deimling, Andreas; Binder, Hans; Weller, Michael; Loeffler, Markus; German Glioma Network.
In: INT J CANCER, Vol. 135, No. 8, 15.10.2014, p. 1822-31.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Molecular characterization of long-term survivors of glioblastoma using genome- and transcriptome-wide profiling
AU - Reifenberger, Guido
AU - Weber, Ruthild G
AU - Riehmer, Vera
AU - Kaulich, Kerstin
AU - Willscher, Edith
AU - Wirth, Henry
AU - Gietzelt, Jens
AU - Hentschel, Bettina
AU - Westphal, Manfred
AU - Simon, Matthias
AU - Schackert, Gabriele
AU - Schramm, Johannes
AU - Matschke, Jakob
AU - Sabel, Michael C
AU - Gramatzki, Dorothee
AU - Felsberg, Jörg
AU - Hartmann, Christian
AU - Steinbach, Joachim P
AU - Schlegel, Uwe
AU - Wick, Wolfgang
AU - Radlwimmer, Bernhard
AU - Pietsch, Torsten
AU - Tonn, Jörg C
AU - von Deimling, Andreas
AU - Binder, Hans
AU - Weller, Michael
AU - Loeffler, Markus
AU - German Glioma Network
N1 - © 2014 UICC.
PY - 2014/10/15
Y1 - 2014/10/15
N2 - The prognosis of glioblastoma, the most malignant type of glioma, is still poor, with only a minority of patients showing long-term survival of more than three years after diagnosis. To elucidate the molecular aberrations in glioblastomas of long-term survivors, we performed genome- and/or transcriptome-wide molecular profiling of glioblastoma samples from 94 patients, including 28 long-term survivors with >36 months overall survival (OS), 20 short-term survivors with <12 months OS and 46 patients with intermediate OS. Integrative bioinformatic analyses were used to characterize molecular aberrations in the distinct survival groups considering established molecular markers such as isocitrate dehydrogenase 1 or 2 (IDH1/2) mutations, and O(6) -methylguanine DNA methyltransferase (MGMT) promoter methylation. Patients with long-term survival were younger and more often had IDH1/2-mutant and MGMT-methylated tumors. Gene expression profiling revealed over-representation of a distinct (proneural-like) expression signature in long-term survivors that was linked to IDH1/2 mutation. However, IDH1/2-wildtype glioblastomas from long-term survivors did not show distinct gene expression profiles and included proneural, classical and mesenchymal glioblastoma subtypes. Genomic imbalances also differed between IDH1/2-mutant and IDH1/2-wildtype tumors, but not between survival groups of IDH1/2-wildtype patients. Thus, our data support an important role for MGMT promoter methylation and IDH1/2 mutation in glioblastoma long-term survival and corroborate the association of IDH1/2 mutation with distinct genomic and transcriptional profiles. Importantly, however, IDH1/2-wildtype glioblastomas in our cohort of long-term survivors lacked distinctive DNA copy number changes and gene expression signatures, indicating that other factors might have been responsible for long survival in this particular subgroup of patients.
AB - The prognosis of glioblastoma, the most malignant type of glioma, is still poor, with only a minority of patients showing long-term survival of more than three years after diagnosis. To elucidate the molecular aberrations in glioblastomas of long-term survivors, we performed genome- and/or transcriptome-wide molecular profiling of glioblastoma samples from 94 patients, including 28 long-term survivors with >36 months overall survival (OS), 20 short-term survivors with <12 months OS and 46 patients with intermediate OS. Integrative bioinformatic analyses were used to characterize molecular aberrations in the distinct survival groups considering established molecular markers such as isocitrate dehydrogenase 1 or 2 (IDH1/2) mutations, and O(6) -methylguanine DNA methyltransferase (MGMT) promoter methylation. Patients with long-term survival were younger and more often had IDH1/2-mutant and MGMT-methylated tumors. Gene expression profiling revealed over-representation of a distinct (proneural-like) expression signature in long-term survivors that was linked to IDH1/2 mutation. However, IDH1/2-wildtype glioblastomas from long-term survivors did not show distinct gene expression profiles and included proneural, classical and mesenchymal glioblastoma subtypes. Genomic imbalances also differed between IDH1/2-mutant and IDH1/2-wildtype tumors, but not between survival groups of IDH1/2-wildtype patients. Thus, our data support an important role for MGMT promoter methylation and IDH1/2 mutation in glioblastoma long-term survival and corroborate the association of IDH1/2 mutation with distinct genomic and transcriptional profiles. Importantly, however, IDH1/2-wildtype glioblastomas in our cohort of long-term survivors lacked distinctive DNA copy number changes and gene expression signatures, indicating that other factors might have been responsible for long survival in this particular subgroup of patients.
KW - Brain Neoplasms
KW - DNA Modification Methylases
KW - DNA Repair Enzymes
KW - Gene Dosage
KW - Gene Expression Profiling
KW - Genome, Human
KW - Glioblastoma
KW - Humans
KW - Isocitrate Dehydrogenase
KW - Mutation
KW - Oligonucleotide Array Sequence Analysis
KW - Promoter Regions, Genetic
KW - Prospective Studies
KW - Survivors
KW - Transcriptome
KW - Tumor Suppressor Proteins
U2 - 10.1002/ijc.28836
DO - 10.1002/ijc.28836
M3 - SCORING: Journal article
C2 - 24615357
VL - 135
SP - 1822
EP - 1831
JO - INT J CANCER
JF - INT J CANCER
SN - 0020-7136
IS - 8
ER -