Long-term survival in primary glioblastoma with versus without isocitrate dehydrogenase mutations
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Long-term survival in primary glioblastoma with versus without isocitrate dehydrogenase mutations. / Hartmann, Christian; Hentschel, Bettina; Simon, Matthias; Westphal, Manfred; Schackert, Gabriele; Tonn, Jörg C; Loeffler, Markus; Reifenberger, Guido; Pietsch, Torsten; von Deimling, Andreas; Weller, Michael; German Glioma Network.
In: CLIN CANCER RES, Vol. 19, No. 18, 15.09.2013, p. 5146-57.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Long-term survival in primary glioblastoma with versus without isocitrate dehydrogenase mutations
AU - Hartmann, Christian
AU - Hentschel, Bettina
AU - Simon, Matthias
AU - Westphal, Manfred
AU - Schackert, Gabriele
AU - Tonn, Jörg C
AU - Loeffler, Markus
AU - Reifenberger, Guido
AU - Pietsch, Torsten
AU - von Deimling, Andreas
AU - Weller, Michael
AU - German Glioma Network
N1 - ©2013 AACR.
PY - 2013/9/15
Y1 - 2013/9/15
N2 - PURPOSE: The determinants of long-term survival in glioblastoma have remained largely obscure. Isocitrate dehydrogenase (IDH) 1 or 2 mutations are common in World Health Organization (WHO) grades II and III gliomas, but rare in primary glioblastomas, and associated with longer survival.EXPERIMENTAL DESIGN: We compared clinical and molecular characteristics of 69 patients with centrally confirmed glioblastoma and survival >36 months (LTS-36), including 33 patients surviving >60 months (LTS-60), with 257 patients surviving <36 months. MGMT promoter methylation, 1p/19q codeletions, EGFR amplification, TP53 mutations, and IDH1/2 mutations were determined by standard techniques.RESULTS: The rate of IDH1/2 mutations in LTS-36 patients was 34% (23 of 67 patients) as opposed to 4.3% in controls (11 of 257 patients). Long-term survivors with IDH1/2-mutant glioblastomas were younger, had almost no EGFR amplifications, but exhibited more often 1p/19q codeletions and TP53 mutations than LTS patients with IDH1/2 wild-type glioblastomas. Long-term survivors with IDH1/2 wild-type showed no distinguishing features from other patients with IDH1/2 wild-type glioblastomas except for a higher rate of MGMT promoter methylation. Similarly, among 11 patients with IDH1/2-mutant glioblastomas without long-term survival, the only difference to IDH1/2-mutant long-term survivors was less-frequent MGMT promoter methylation. Compared with LTS-36 patients, LTS-60 patients had less frequently TP53 mutations and radiotherapy alone as initial treatment.CONCLUSIONS: IDH1/2 mutations define a subgroup of tumors of LTS patients that exhibit molecular characteristics of WHO grade II/III gliomas and secondary glioblastomas. Determinants of LTS with IDH1/2 wild-type glioblastomas, which exhibit typical molecular features of primary glioblastomas, beyond MGMT promoter methylation, remain to be identified.
AB - PURPOSE: The determinants of long-term survival in glioblastoma have remained largely obscure. Isocitrate dehydrogenase (IDH) 1 or 2 mutations are common in World Health Organization (WHO) grades II and III gliomas, but rare in primary glioblastomas, and associated with longer survival.EXPERIMENTAL DESIGN: We compared clinical and molecular characteristics of 69 patients with centrally confirmed glioblastoma and survival >36 months (LTS-36), including 33 patients surviving >60 months (LTS-60), with 257 patients surviving <36 months. MGMT promoter methylation, 1p/19q codeletions, EGFR amplification, TP53 mutations, and IDH1/2 mutations were determined by standard techniques.RESULTS: The rate of IDH1/2 mutations in LTS-36 patients was 34% (23 of 67 patients) as opposed to 4.3% in controls (11 of 257 patients). Long-term survivors with IDH1/2-mutant glioblastomas were younger, had almost no EGFR amplifications, but exhibited more often 1p/19q codeletions and TP53 mutations than LTS patients with IDH1/2 wild-type glioblastomas. Long-term survivors with IDH1/2 wild-type showed no distinguishing features from other patients with IDH1/2 wild-type glioblastomas except for a higher rate of MGMT promoter methylation. Similarly, among 11 patients with IDH1/2-mutant glioblastomas without long-term survival, the only difference to IDH1/2-mutant long-term survivors was less-frequent MGMT promoter methylation. Compared with LTS-36 patients, LTS-60 patients had less frequently TP53 mutations and radiotherapy alone as initial treatment.CONCLUSIONS: IDH1/2 mutations define a subgroup of tumors of LTS patients that exhibit molecular characteristics of WHO grade II/III gliomas and secondary glioblastomas. Determinants of LTS with IDH1/2 wild-type glioblastomas, which exhibit typical molecular features of primary glioblastomas, beyond MGMT promoter methylation, remain to be identified.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Brain Neoplasms
KW - Cohort Studies
KW - Combined Modality Therapy
KW - DNA Methylation
KW - DNA Modification Methylases
KW - DNA Repair Enzymes
KW - DNA, Neoplasm
KW - Female
KW - Follow-Up Studies
KW - Gene Amplification
KW - Glioblastoma
KW - Humans
KW - Isocitrate Dehydrogenase
KW - Male
KW - Middle Aged
KW - Mutation
KW - Neoplasm Staging
KW - Polymerase Chain Reaction
KW - Prognosis
KW - Promoter Regions, Genetic
KW - Receptor, Epidermal Growth Factor
KW - Survival Rate
KW - Survivors
KW - Tumor Suppressor Protein p53
KW - Tumor Suppressor Proteins
KW - Young Adult
U2 - 10.1158/1078-0432.CCR-13-0017
DO - 10.1158/1078-0432.CCR-13-0017
M3 - SCORING: Journal article
C2 - 23918605
VL - 19
SP - 5146
EP - 5157
JO - CLIN CANCER RES
JF - CLIN CANCER RES
SN - 1078-0432
IS - 18
ER -