Genomic aberrations associated with outcome in anaplastic oligodendroglial tumors treated within the EORTC phase III trial 26951

Ahmed Idbaih, Cyril Dalmasso, Mathilde Kouwenhoven, Judith Jeuken, Catherine Carpentier, Thierry Gorlia, Johan M Kros, Pim French, Johannes Teepen, Philippe Broët, Olivier Delattre, Karima Mokhtari, Marc Sanson, Jean-Yves Delattre, Martin van den Bent, Khê Hoang-Xuan

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Despite similar morphological aspects, anaplastic oligodendroglial tumors (AOTs) form a heterogeneous clinical subgroup of gliomas. The chromosome arms 1p/19q codeletion has been shown to be a relevant biomarker in AOTs and to be perfectly exclusive from EGFR amplification in gliomas. To identify new genomic regions associated with prognosis, 60 AOTs from the EORTC trial 26951 were analyzed retrospectively using BAC-array-based comparative genomic hybridization. The data were processed using a binary tree method. Thirty-three BACs with prognostic value were identified distinguishing four genomic subgroups of AOTs with different prognosis (p < 0.0001). Type I tumors (25%) were characterized by: (1) an EGFR amplification, (2) a poor prognosis, (3) a higher rate of necrosis, and (4) an older age of patients. Type II tumors (21.7%) had: (1) loss of prognostic BACs located on 1p tightly associated with 19q deletion, (2) a longer survival, (3) an oligodendroglioma phenotype, and (4) a frontal location in brain. Type III AOTs (11.7%) exhibited: (1) a deletion of prognostic BACs located on 21q, and (2) a short survival. Finally, type IV tumors (41.7%) had different genomic patterns and prognosis than type I, II and III AOTs. Multivariate analysis showed that genomic type provides additional prognostic data to clinical, imaging and pathological features. Similar results were obtained in the cohort of 45 centrally reviewed-validated cases of AOTs. Whole genome analysis appears useful to screen the numerous genomic abnormalities observed in AOTs and to propose new biomarkers particularly in the non-1p/19q codeleted AOTs.

Original languageEnglish
Pages (from-to)221-30
Number of pages10
JournalJournal of Neuro-Oncology
Volume103
Issue number2
DOIs
Publication statusPublished - Jun 2011

Cite this

Idbaih, Ahmed ; Dalmasso, Cyril ; Kouwenhoven, Mathilde ; Jeuken, Judith ; Carpentier, Catherine ; Gorlia, Thierry ; Kros, Johan M ; French, Pim ; Teepen, Johannes ; Broët, Philippe ; Delattre, Olivier ; Mokhtari, Karima ; Sanson, Marc ; Delattre, Jean-Yves ; van den Bent, Martin ; Hoang-Xuan, Khê. / Genomic aberrations associated with outcome in anaplastic oligodendroglial tumors treated within the EORTC phase III trial 26951. In: Journal of Neuro-Oncology. 2011 ; Vol. 103, No. 2. pp. 221-30.
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abstract = "Despite similar morphological aspects, anaplastic oligodendroglial tumors (AOTs) form a heterogeneous clinical subgroup of gliomas. The chromosome arms 1p/19q codeletion has been shown to be a relevant biomarker in AOTs and to be perfectly exclusive from EGFR amplification in gliomas. To identify new genomic regions associated with prognosis, 60 AOTs from the EORTC trial 26951 were analyzed retrospectively using BAC-array-based comparative genomic hybridization. The data were processed using a binary tree method. Thirty-three BACs with prognostic value were identified distinguishing four genomic subgroups of AOTs with different prognosis (p < 0.0001). Type I tumors (25{\%}) were characterized by: (1) an EGFR amplification, (2) a poor prognosis, (3) a higher rate of necrosis, and (4) an older age of patients. Type II tumors (21.7{\%}) had: (1) loss of prognostic BACs located on 1p tightly associated with 19q deletion, (2) a longer survival, (3) an oligodendroglioma phenotype, and (4) a frontal location in brain. Type III AOTs (11.7{\%}) exhibited: (1) a deletion of prognostic BACs located on 21q, and (2) a short survival. Finally, type IV tumors (41.7{\%}) had different genomic patterns and prognosis than type I, II and III AOTs. Multivariate analysis showed that genomic type provides additional prognostic data to clinical, imaging and pathological features. Similar results were obtained in the cohort of 45 centrally reviewed-validated cases of AOTs. Whole genome analysis appears useful to screen the numerous genomic abnormalities observed in AOTs and to propose new biomarkers particularly in the non-1p/19q codeleted AOTs.",
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author = "Ahmed Idbaih and Cyril Dalmasso and Mathilde Kouwenhoven and Judith Jeuken and Catherine Carpentier and Thierry Gorlia and Kros, {Johan M} and Pim French and Johannes Teepen and Philippe Bro{\"e}t and Olivier Delattre and Karima Mokhtari and Marc Sanson and Jean-Yves Delattre and {van den Bent}, Martin and Kh{\^e} Hoang-Xuan",
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Idbaih, A, Dalmasso, C, Kouwenhoven, M, Jeuken, J, Carpentier, C, Gorlia, T, Kros, JM, French, P, Teepen, J, Broët, P, Delattre, O, Mokhtari, K, Sanson, M, Delattre, J-Y, van den Bent, M & Hoang-Xuan, K 2011, 'Genomic aberrations associated with outcome in anaplastic oligodendroglial tumors treated within the EORTC phase III trial 26951' Journal of Neuro-Oncology, vol. 103, no. 2, pp. 221-30. https://doi.org/10.1007/s11060-010-0380-9

Genomic aberrations associated with outcome in anaplastic oligodendroglial tumors treated within the EORTC phase III trial 26951. / Idbaih, Ahmed; Dalmasso, Cyril; Kouwenhoven, Mathilde; Jeuken, Judith; Carpentier, Catherine; Gorlia, Thierry; Kros, Johan M; French, Pim; Teepen, Johannes; Broët, Philippe; Delattre, Olivier; Mokhtari, Karima; Sanson, Marc; Delattre, Jean-Yves; van den Bent, Martin; Hoang-Xuan, Khê.

In: Journal of Neuro-Oncology, Vol. 103, No. 2, 06.2011, p. 221-30.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Genomic aberrations associated with outcome in anaplastic oligodendroglial tumors treated within the EORTC phase III trial 26951

AU - Idbaih, Ahmed

AU - Dalmasso, Cyril

AU - Kouwenhoven, Mathilde

AU - Jeuken, Judith

AU - Carpentier, Catherine

AU - Gorlia, Thierry

AU - Kros, Johan M

AU - French, Pim

AU - Teepen, Johannes

AU - Broët, Philippe

AU - Delattre, Olivier

AU - Mokhtari, Karima

AU - Sanson, Marc

AU - Delattre, Jean-Yves

AU - van den Bent, Martin

AU - Hoang-Xuan, Khê

PY - 2011/6

Y1 - 2011/6

N2 - Despite similar morphological aspects, anaplastic oligodendroglial tumors (AOTs) form a heterogeneous clinical subgroup of gliomas. The chromosome arms 1p/19q codeletion has been shown to be a relevant biomarker in AOTs and to be perfectly exclusive from EGFR amplification in gliomas. To identify new genomic regions associated with prognosis, 60 AOTs from the EORTC trial 26951 were analyzed retrospectively using BAC-array-based comparative genomic hybridization. The data were processed using a binary tree method. Thirty-three BACs with prognostic value were identified distinguishing four genomic subgroups of AOTs with different prognosis (p < 0.0001). Type I tumors (25%) were characterized by: (1) an EGFR amplification, (2) a poor prognosis, (3) a higher rate of necrosis, and (4) an older age of patients. Type II tumors (21.7%) had: (1) loss of prognostic BACs located on 1p tightly associated with 19q deletion, (2) a longer survival, (3) an oligodendroglioma phenotype, and (4) a frontal location in brain. Type III AOTs (11.7%) exhibited: (1) a deletion of prognostic BACs located on 21q, and (2) a short survival. Finally, type IV tumors (41.7%) had different genomic patterns and prognosis than type I, II and III AOTs. Multivariate analysis showed that genomic type provides additional prognostic data to clinical, imaging and pathological features. Similar results were obtained in the cohort of 45 centrally reviewed-validated cases of AOTs. Whole genome analysis appears useful to screen the numerous genomic abnormalities observed in AOTs and to propose new biomarkers particularly in the non-1p/19q codeleted AOTs.

AB - Despite similar morphological aspects, anaplastic oligodendroglial tumors (AOTs) form a heterogeneous clinical subgroup of gliomas. The chromosome arms 1p/19q codeletion has been shown to be a relevant biomarker in AOTs and to be perfectly exclusive from EGFR amplification in gliomas. To identify new genomic regions associated with prognosis, 60 AOTs from the EORTC trial 26951 were analyzed retrospectively using BAC-array-based comparative genomic hybridization. The data were processed using a binary tree method. Thirty-three BACs with prognostic value were identified distinguishing four genomic subgroups of AOTs with different prognosis (p < 0.0001). Type I tumors (25%) were characterized by: (1) an EGFR amplification, (2) a poor prognosis, (3) a higher rate of necrosis, and (4) an older age of patients. Type II tumors (21.7%) had: (1) loss of prognostic BACs located on 1p tightly associated with 19q deletion, (2) a longer survival, (3) an oligodendroglioma phenotype, and (4) a frontal location in brain. Type III AOTs (11.7%) exhibited: (1) a deletion of prognostic BACs located on 21q, and (2) a short survival. Finally, type IV tumors (41.7%) had different genomic patterns and prognosis than type I, II and III AOTs. Multivariate analysis showed that genomic type provides additional prognostic data to clinical, imaging and pathological features. Similar results were obtained in the cohort of 45 centrally reviewed-validated cases of AOTs. Whole genome analysis appears useful to screen the numerous genomic abnormalities observed in AOTs and to propose new biomarkers particularly in the non-1p/19q codeleted AOTs.

KW - Adult

KW - Aged

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Biomarkers, Tumor/analysis

KW - Brain Neoplasms/drug therapy

KW - Chromosome Aberrations

KW - Chromosomes, Artificial, Bacterial

KW - Combined Modality Therapy

KW - Comparative Genomic Hybridization

KW - Humans

KW - In Situ Hybridization, Fluorescence

KW - Kaplan-Meier Estimate

KW - Lomustine/administration & dosage

KW - Male

KW - Middle Aged

KW - Multicenter Studies as Topic

KW - Oligodendroglioma/drug therapy

KW - Procarbazine/administration & dosage

KW - Prognosis

KW - Proportional Hazards Models

KW - Radiotherapy

KW - Retrospective Studies

KW - Treatment Outcome

KW - Vincristine/administration & dosage

KW - Young Adult

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DO - 10.1007/s11060-010-0380-9

M3 - Article

VL - 103

SP - 221

EP - 230

JO - Journal of Neuro-Oncology

JF - Journal of Neuro-Oncology

SN - 0167-594X

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