IDH1 and IDH2 Mutations Are Prognostic but not Predictive for Outcome in Anaplastic Oligodendroglial Tumors: A Report of the European Organization for Research and Treatment of Cancer Brain Tumor Group (2024)

van den Bent, M., Dubbink, E. J., Marie, Y., Brandes, AA., Taphoorn, MJB., Wesseling, P., Frenay, M., Tijssen, CC., Lacombe, D., Idbaih, A., van Marion, R., Kros, J. M., Dinjens, W., Gorlia, T., & Sanson, M. (2010). IDH1 and IDH2 Mutations Are Prognostic but not Predictive for Outcome in Anaplastic Oligodendroglial Tumors: A Report of the European Organization for Research and Treatment of Cancer Brain Tumor Group. Clinical Cancer Research, 16(5), 1597-1604. https://doi.org/10.1158/1078-0432.CCR-09-2902

van den Bent, Martin ; Dubbink, Erik jan ; Marie, Y et al. / IDH1 and IDH2 Mutations Are Prognostic but not Predictive for Outcome in Anaplastic Oligodendroglial Tumors: A Report of the European Organization for Research and Treatment of Cancer Brain Tumor Group. In: Clinical Cancer Research. 2010 ; Vol. 16, No. 5. pp. 1597-1604.

@article{35f5c4673c90434c8e521dc61bcc40c2,

title = "IDH1 and IDH2 Mutations Are Prognostic but not Predictive for Outcome in Anaplastic Oligodendroglial Tumors: A Report of the European Organization for Research and Treatment of Cancer Brain Tumor Group",

abstract = "Purpose: Recent studies have shown the prognostic significance of IDH1 mutations in glioma. It is yet unclear if IDH1 mutations are predictive for outcome to chemotherapy. We determined the effect of IDH1 mutations on progression-free survival and overall survival (OS), and its correlation with other clinical and molecular features in the prospective randomized European Organization for Research and Treatment of Cancer study 26951 on adjuvant procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-L-nitrosourea, and vincristine (PCV) in anaplastic oligodendroglioma. Experimental Design: IDH1 and IDH2 alterations of the mutational hotspot codons R132 and R172 were assessed by the bidirectional cycle sequencing of PCR-amplified fragments. MGMT promoter methylation was assessed using methylation-specific multiplex ligation-dependant probe amplification based on methylation-sensitive restriction analysis. Loss of chromosomes 1p, 19q, 10, and 10q and the gain of 7 and the EGFR gene were assessed with fluorescence in situ hybridization. Results: From 159 patients, sufficient material was available for IDH1 analysis. In 151 and 118 of these patients, respectively, the 1p/19q status and the MGMT promoter methylation status were known. In 73 cases (46%), an IDH1 mutation was found and only one IDH2 mutation was identified. The presence of IDH1 mutations correlated with 1p/19q codeletion and MGMT promoter methylation, and inversely correlated with loss of chromosome 10, EGFR amplification, polysomy of chromosome 7, and the presence of necrosis. IDH1 mutations were found to be prognostic in the radiotherapy-and the radiotherapy/PCV-treated patients, for both progression-free survival and OS. With Cox proportional hazard modeling for OS with stepwise selection, IDH1 mutations and 1p/19q codeletion but not MGMT promoter methylation were independent prognostic factors. Conclusion: In this hom*ogeneously treated group of anaplastic oligodendroglioma patients, the presence of IDH1 mutations was found to carry a very strong prognostic significance for OS but without evidence of a predictive significance for outcome to PCV chemotherapy. IDH1 mutations were strongly associated with 1p/19q codeletion and MGMT promoter methylation. Clin Cancer Res; 16(5); 1597-604. (C) 2010 AACR.",

author = "{van den Bent}, Martin and Dubbink, {Erik jan} and Y Marie and AA Brandes and MJB Taphoorn and P Wesseling and M Frenay and CC Tijssen and D Lacombe and A Idbaih and {van Marion}, Ronald and J.M. Kros and Winand Dinjens and T Gorlia and M Sanson",

year = "2010",

doi = "10.1158/1078-0432.CCR-09-2902",

language = "Undefined/Unknown",

volume = "16",

pages = "1597--1604",

journal = "Clinical Cancer Research",

issn = "1078-0432",

publisher = "American Association for Cancer Research Inc.",

number = "5",

}

van den Bent, M, Dubbink, EJ, Marie, Y, Brandes, AA, Taphoorn, MJB, Wesseling, P, Frenay, M, Tijssen, CC, Lacombe, D, Idbaih, A, van Marion, R, Kros, JM, Dinjens, W, Gorlia, T & Sanson, M 2010, 'IDH1 and IDH2 Mutations Are Prognostic but not Predictive for Outcome in Anaplastic Oligodendroglial Tumors: A Report of the European Organization for Research and Treatment of Cancer Brain Tumor Group', Clinical Cancer Research, vol. 16, no. 5, pp. 1597-1604. https://doi.org/10.1158/1078-0432.CCR-09-2902

IDH1 and IDH2 Mutations Are Prognostic but not Predictive for Outcome in Anaplastic Oligodendroglial Tumors: A Report of the European Organization for Research and Treatment of Cancer Brain Tumor Group. / van den Bent, Martin; Dubbink, Erik jan; Marie, Y et al.
In: Clinical Cancer Research, Vol. 16, No. 5, 2010, p. 1597-1604.

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

TY - JOUR

T1 - IDH1 and IDH2 Mutations Are Prognostic but not Predictive for Outcome in Anaplastic Oligodendroglial Tumors: A Report of the European Organization for Research and Treatment of Cancer Brain Tumor Group

AU - van den Bent, Martin

AU - Dubbink, Erik jan

AU - Marie, Y

AU - Brandes, AA

AU - Taphoorn, MJB

AU - Wesseling, P

AU - Frenay, M

AU - Tijssen, CC

AU - Lacombe, D

AU - Idbaih, A

AU - van Marion, Ronald

AU - Kros, J.M.

AU - Dinjens, Winand

AU - Gorlia, T

AU - Sanson, M

PY - 2010

Y1 - 2010

N2 - Purpose: Recent studies have shown the prognostic significance of IDH1 mutations in glioma. It is yet unclear if IDH1 mutations are predictive for outcome to chemotherapy. We determined the effect of IDH1 mutations on progression-free survival and overall survival (OS), and its correlation with other clinical and molecular features in the prospective randomized European Organization for Research and Treatment of Cancer study 26951 on adjuvant procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-L-nitrosourea, and vincristine (PCV) in anaplastic oligodendroglioma. Experimental Design: IDH1 and IDH2 alterations of the mutational hotspot codons R132 and R172 were assessed by the bidirectional cycle sequencing of PCR-amplified fragments. MGMT promoter methylation was assessed using methylation-specific multiplex ligation-dependant probe amplification based on methylation-sensitive restriction analysis. Loss of chromosomes 1p, 19q, 10, and 10q and the gain of 7 and the EGFR gene were assessed with fluorescence in situ hybridization. Results: From 159 patients, sufficient material was available for IDH1 analysis. In 151 and 118 of these patients, respectively, the 1p/19q status and the MGMT promoter methylation status were known. In 73 cases (46%), an IDH1 mutation was found and only one IDH2 mutation was identified. The presence of IDH1 mutations correlated with 1p/19q codeletion and MGMT promoter methylation, and inversely correlated with loss of chromosome 10, EGFR amplification, polysomy of chromosome 7, and the presence of necrosis. IDH1 mutations were found to be prognostic in the radiotherapy-and the radiotherapy/PCV-treated patients, for both progression-free survival and OS. With Cox proportional hazard modeling for OS with stepwise selection, IDH1 mutations and 1p/19q codeletion but not MGMT promoter methylation were independent prognostic factors. Conclusion: In this hom*ogeneously treated group of anaplastic oligodendroglioma patients, the presence of IDH1 mutations was found to carry a very strong prognostic significance for OS but without evidence of a predictive significance for outcome to PCV chemotherapy. IDH1 mutations were strongly associated with 1p/19q codeletion and MGMT promoter methylation. Clin Cancer Res; 16(5); 1597-604. (C) 2010 AACR.

AB - Purpose: Recent studies have shown the prognostic significance of IDH1 mutations in glioma. It is yet unclear if IDH1 mutations are predictive for outcome to chemotherapy. We determined the effect of IDH1 mutations on progression-free survival and overall survival (OS), and its correlation with other clinical and molecular features in the prospective randomized European Organization for Research and Treatment of Cancer study 26951 on adjuvant procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-L-nitrosourea, and vincristine (PCV) in anaplastic oligodendroglioma. Experimental Design: IDH1 and IDH2 alterations of the mutational hotspot codons R132 and R172 were assessed by the bidirectional cycle sequencing of PCR-amplified fragments. MGMT promoter methylation was assessed using methylation-specific multiplex ligation-dependant probe amplification based on methylation-sensitive restriction analysis. Loss of chromosomes 1p, 19q, 10, and 10q and the gain of 7 and the EGFR gene were assessed with fluorescence in situ hybridization. Results: From 159 patients, sufficient material was available for IDH1 analysis. In 151 and 118 of these patients, respectively, the 1p/19q status and the MGMT promoter methylation status were known. In 73 cases (46%), an IDH1 mutation was found and only one IDH2 mutation was identified. The presence of IDH1 mutations correlated with 1p/19q codeletion and MGMT promoter methylation, and inversely correlated with loss of chromosome 10, EGFR amplification, polysomy of chromosome 7, and the presence of necrosis. IDH1 mutations were found to be prognostic in the radiotherapy-and the radiotherapy/PCV-treated patients, for both progression-free survival and OS. With Cox proportional hazard modeling for OS with stepwise selection, IDH1 mutations and 1p/19q codeletion but not MGMT promoter methylation were independent prognostic factors. Conclusion: In this hom*ogeneously treated group of anaplastic oligodendroglioma patients, the presence of IDH1 mutations was found to carry a very strong prognostic significance for OS but without evidence of a predictive significance for outcome to PCV chemotherapy. IDH1 mutations were strongly associated with 1p/19q codeletion and MGMT promoter methylation. Clin Cancer Res; 16(5); 1597-604. (C) 2010 AACR.

U2 - 10.1158/1078-0432.CCR-09-2902

DO - 10.1158/1078-0432.CCR-09-2902

M3 - Article

C2 - 20160062

SN - 1078-0432

VL - 16

SP - 1597

EP - 1604

JO - Clinical Cancer Research

JF - Clinical Cancer Research

IS - 5

ER -

van den Bent M, Dubbink EJ, Marie Y, Brandes AA, Taphoorn MJB, Wesseling P et al. IDH1 and IDH2 Mutations Are Prognostic but not Predictive for Outcome in Anaplastic Oligodendroglial Tumors: A Report of the European Organization for Research and Treatment of Cancer Brain Tumor Group. Clinical Cancer Research. 2010;16(5):1597-1604. doi: 10.1158/1078-0432.CCR-09-2902