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
U2 - 10.1007/s11060-010-0380-9
DO - 10.1007/s11060-010-0380-9
M3 - Article
C2 - 20820870
VL - 103
SP - 221
EP - 230
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
SN - 0167-594X
IS - 2
ER -