%0 Journal Article %1 Hartmann.2013 %A Hartmann, Christian %A Hentschel, Bettina %A Simon, Matthias %A Westphal, Manfred %A Schackert, Gabriele %A Tonn, Jörg C. %A Loeffler, Markus %A Reifenberger, Guido %A Pietsch, Torsten %A Deimling, Andreas von %A Weller, Michael %D 2013 %J Clinical cancer research : an official journal of the American Association for Cancer Research %K Adult Aged Aged,_80_and_over Brain_Neoplasms/genetics/mortality/pathology/therapy Cohort_Studies Combined_Modality_Therapy DNA_Methylation DNA_Modification_Methylases/genetics DNA_Repair_Enzymes/genetics DNA,_Neoplasm/genetics Female Follow-Up_Studies Gene_Amplification Glioblastoma/genetics/mortality/pathology/therapy Humans Isocitrate_Dehydrogenase/genetics Male Middle_Aged Mutation/genetics Neoplasm_Staging Polymerase_Chain_Reaction Prognosis Promoter_Regions,_Genetic/genetics Receptor,_Epidermal_Growth_Factor/genetics Survival_Rate Survivors Tumor_Suppressor_Protein_p53/genetics Tumor_Suppressor_Proteins/genetics Young_Adult %N 18 %P 5146–5157 %T Long-term survival in primary glioblastoma with versus without isocitrate dehydrogenase mutations %V 19 %X PURPOSE\r\nThe 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.\r\nEXPERIMENTAL DESIGN\r\nWe 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.\r\nRESULTS\r\nThe 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.\r\nCONCLUSIONS\r\nIDH1/2 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.

@article{Hartmann.2013, abstract = {PURPOSE\r\nThe 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.\r\nEXPERIMENTAL DESIGN\r\nWe 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.\r\nRESULTS\r\nThe 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.\r\nCONCLUSIONS\r\nIDH1/2 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.}, added-at = {2014-10-13T18:24:49.000+0200}, author = {Hartmann, Christian and Hentschel, Bettina and Simon, Matthias and Westphal, Manfred and Schackert, Gabriele and Tonn, Jörg C. and Loeffler, Markus and Reifenberger, Guido and Pietsch, Torsten and Deimling, Andreas von and Weller, Michael}, biburl = {https://www.bibsonomy.org/bibtex/239fcd89b3df752be88507e90d15fe2c9/drtester}, interhash = {cd1cb2b97e2a98d3aefd17346fc9ee88}, intrahash = {39fcd89b3df752be88507e90d15fe2c9}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, keywords = {Adult Aged Aged,_80_and_over Brain_Neoplasms/genetics/mortality/pathology/therapy Cohort_Studies Combined_Modality_Therapy DNA_Methylation DNA_Modification_Methylases/genetics DNA_Repair_Enzymes/genetics DNA,_Neoplasm/genetics Female Follow-Up_Studies Gene_Amplification Glioblastoma/genetics/mortality/pathology/therapy Humans Isocitrate_Dehydrogenase/genetics Male Middle_Aged Mutation/genetics Neoplasm_Staging Polymerase_Chain_Reaction Prognosis Promoter_Regions,_Genetic/genetics Receptor,_Epidermal_Growth_Factor/genetics Survival_Rate Survivors Tumor_Suppressor_Protein_p53/genetics Tumor_Suppressor_Proteins/genetics Young_Adult}, number = 18, pages = {5146–5157}, timestamp = {2014-10-13T18:24:49.000+0200}, title = {Long-term survival in primary glioblastoma with versus without isocitrate dehydrogenase mutations}, volume = 19, year = 2013 }