BAC array CGH distinguishes mutually exclusive alterations that define clinicogenetic subtypes of gliomas.
The pathological classification of gliomas constitutes a critical step of the clinical management of patients, yet it is frequently challenging. To assess the relationship between genetic abnormalities and clinicopathological characteristics, we have performed a genetic and clinical analysis of a series of gliomas. A total of 112 gliomas were analyzed by comparative genomic hybridization on a BAC array with a 1 megabase resolution. Altered regions were identified and correlation analysis enabled to retrieve significant associations and exclusions. Whole chromosomes (chrs) 1p and 19q losses with centromeric breakpoints and EGFR high level amplification were found to be mutually exclusive, permitting identification of 3 distinct, nonoverlapping groups of tumors with striking clinicopathological differences. Type A tumors with chrs 1p and 19q co-deletion exhibited an oligodendroglial phenotype and a longer patient survival. Type B tumors were characterized by EGFR amplification. They harbored a WHO high grade of malignancy and a short patient survival. Finally, type C tumors displayed none of the previous patterns but the presence of chr 7 gain, chr 9p deletion and/or chr 10 loss. It included astrocytic tumors in patients younger than in type B and whose prognosis was highly dependent upon the number of alterations. A multivariate analysis based on a Cox model shows that age, WHO grade and genomic type provide complementary prognostic informations. Finally, our results highlight the potential of a whole-genome analysis as an additional diagnostic in cases of unclear conventional genetic findings.
Idbaih
Ahmed
A
INSERM, Unité 830, Paris, France.
Marie
Yannick
Y
Lucchesi
Carlo
C
Pierron
Gaëlle
G
Manié
Elodie
E
Raynal
Virginie
V
Mosseri
Véronique
V
Hoang-Xuan
Khê
K
Kujas
Michèle
M
Brito
Isabel
I
Mokhtari
Karima
K
Sanson
Marc
M
Barillot
Emmanuel
E
Aurias
Alain
A
Delattre
Jean-Yves
JY
Delattre
Olivier
O
D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000235:genetics / Q000473:pathology; D001932:Brain Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D002872:Chromosome Deletion; D022202:Chromosomes, Artificial, Bacterial; D002878:Chromosomes, Human, Pair 1; D002879:Chromosomes, Human, Pair 10; D002888:Chromosomes, Human, Pair 19; D002897:Chromosomes, Human, Pair 7; D002899:Chromosomes, Human, Pair 9; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005910:Glioma / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009693:Nucleic Acid Hybridization; D009837:Oligodendroglioma / Q000235:genetics / Q000473:pathology; D009841:Oligonucleotides; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis; D014944:World Health Organization
D009841:Oligonucleotides; D066246:ErbB Receptors