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BAC array CGH distinguishes mutually exclusive alterations that define clinicogenetic subtypes of gliomas
Author(s) -
Idbaih Ahmed,
Marie Yannick,
Lucchesi Carlo,
Pierron Gaëlle,
Manié Elodie,
Raynal Virginie,
Mosseri Véronique,
HoangXuan Khê,
Kujas Michèle,
Brito Isabel,
Mokhtari Karima,
Sanson Marc,
Barillot Emmanuel,
Aurias Alain,
Delattre JeanYves,
Delattre Olivier
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23270
Subject(s) - comparative genomic hybridization , breakpoint , malignancy , biology , copy number analysis , pathological , phenotype , glioma , genome , pathology , genetics , copy number variation , medicine , gene , chromosomal translocation
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 codeletion 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. © 2007 Wiley‐Liss, Inc.