Specific chromosomal imbalances as detected by array CGH in ependymomas in association with tumor location, histological subtype and grade.
Ependymomas are glial neoplasms originating from the wall of the ventricles or from the spinal canal. The significance of histopathological features in accurately predicting biological behavior is still debated. Moreover, key molecular events in the pathogenesis of ependymoma are yet to be defined. The main objective of the present study was to identify specific patterns of chromosomal aberrations that correlate with tumor location, histological subtype and grade. Forty-five ependymoma samples were analyzed by 1-megabase resolution array comparative genomic hybridization (CGH). Association between clinical or histopathological parameters and the genomic alterations identified was evaluated. The most frequently detected chromosome (chr) abnormalities were gain of chr 7, 9, 12 and 15 and loss of chr 22. Co-occurrence of those five alterations characterized spinal ependymomas (P = 0.01). Myxopapillary ependymomas displayed a specific genomic profile defined by concurrent gain of chr 5, 7, 9, 16 and 18 (P = 0.0007). Overall, the number of chromosomal abnormalities detected was inversely correlated with the malignancy grade. Gain of chr 1q correlated with intracranial high-grade tumors (P = 0.002). Loss of chr 6q was mainly observed in infratentorial (P = 0.02) and World Health Organization (WHO) grade III (P = 0.04) lesions. Chr 10q loss was associated with high-grade ependymomas (P = 0.01). The +7/+9/+12/+15/-22 genomic profile is significantly associated with WHO grade II spinal ependymomas, whereas the +5/+7/+9/+16/+18 genomic pattern is specific of myxopapillary ependymomas. Identification of specific genomic imbalances at a given tumor location suggests that ependymomas from different central nervous system (CNS) regions represent genetically distinct diseases. Detecting genomic alterations associated with aggressive biological behavior may help stratify patients in high- and low-risk disease.
UPMC - INSERM U711 Neuro-Oncologie expérimentale, Paris, France. audrey.rousseau@psl.aphp.fr
Audrey
A
Rousseau
Ahmed
A
Idbaih
François
F
Ducray
Emmanuelle
E
Crinière
Michèle
M
Fèvre-Montange
Anne
A
Jouvet
Jean-Yves
JY
Delattre
D000293:Adolescent; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000145:classification / Q000235:genetics / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations / Q000145:classification; D002875:Chromosomes; D055028:Comparative Genomic Hybridization / Q000379:methods; D004806:Ependymoma / Q000145:classification / Q000235:genetics / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D055815:Young Adult