title: Genomic aberrations associated with outcome in anaplastic oligodendroglial tumors treated within the EORTC phase III trial 26951.
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.
authors.affiliation: INSERM, U975, Université Pierre & Marie Curie Paris VI, Faculté de médecine Pitié-Salpêtrière, CNRS UMR 7225, Paris, France. ahmed.idbaih@gmail.com
authors.forename: Ahmed
authors.initials: A
authors.lastname: Idbaih
authors.forename: Cyril
authors.initials: C
authors.lastname: Dalmasso
authors.forename: Mathilde
authors.initials: M
authors.lastname: Kouwenhoven
authors.forename: Judith
authors.initials: J
authors.lastname: Jeuken
authors.forename: Catherine
authors.initials: C
authors.lastname: Carpentier
authors.forename: Thierry
authors.initials: T
authors.lastname: Gorlia
authors.forename: Johan M
authors.initials: JM
authors.lastname: Kros
authors.forename: Pim
authors.initials: P
authors.lastname: French
authors.forename: Johannes
authors.initials: J
authors.lastname: Teepen
authors.forename: Philippe
authors.initials: P
authors.lastname: Broët
authors.forename: Olivier
authors.initials: O
authors.lastname: Delattre
authors.forename: Karima
authors.initials: K
authors.lastname: Mokhtari
authors.forename: Marc
authors.initials: M
authors.lastname: Sanson
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Delattre
authors.forename: Martin
authors.initials: M
authors.lastname: van den Bent
authors.forename: Khê
authors.initials: K
authors.lastname: Hoang-Xuan
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D002869:Chromosome Aberrations; D022202:Chromosomes, Artificial, Bacterial; D003131:Combined Modality Therapy; D055028:Comparative Genomic Hybridization; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008130:Lomustine / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009837:Oligodendroglioma / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D011344:Procarbazine / Q000008:administration & dosage; D011379:Prognosis; D016016:Proportional Hazards Models; D011878:Radiotherapy; D012189:Retrospective Studies; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D011344:Procarbazine; D014750:Vincristine; D008130:Lomustine
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