Genomic aberrations associated with outcome in anaplastic oligodendroglial tumors treated within the EORTC phase III trial 26951.
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.
Idbaih
Ahmed
A
INSERM, U975, Université Pierre & Marie Curie Paris VI, Faculté de médecine Pitié-Salpêtrière, CNRS UMR 7225, Paris, France. ahmed.idbaih@gmail.com
Dalmasso
Cyril
C
Kouwenhoven
Mathilde
M
Jeuken
Judith
J
Carpentier
Catherine
C
Gorlia
Thierry
T
Kros
Johan M
JM
French
Pim
P
Teepen
Johannes
J
Broët
Philippe
P
Delattre
Olivier
O
Mokhtari
Karima
K
Sanson
Marc
M
Delattre
Jean-Yves
JY
van den Bent
Martin
M
Hoang-Xuan
Khê
K
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
D014408:Biomarkers, Tumor; D011344:Procarbazine; D014750:Vincristine; D008130:Lomustine
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