BAC array CGH distinguishes mutually exclusive alterations that define clinicogenetic subtypes of gliomas

• Published in: International journal of cancer Vol. 122; no. 8; pp. 1778 - 1786
• Main Authors: Idbaih, Ahmed, Marie, Yannick, Lucchesi, Carlo, Pierron, Gaëlle, Manié, Elodie, Raynal, Virginie, Mosseri, Véronique, Hoang‐Xuan, Khê, Kujas, Michèle, Brito, Isabel, Mokhtari, Karima, Sanson, Marc, Barillot, Emmanuel, Aurias, Alain, Delattre, Jean‐Yves, Delattre, Olivier
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.04.2008; Wiley-Liss; Wiley
• Subjects: Adult; Aged; Astrocytoma; Astrocytoma - genetics; Astrocytoma - pathology; BAC array CGH; Biological and medical sciences; Brain Neoplasms; Brain Neoplasms - classification; Brain Neoplasms - genetics; Brain Neoplasms - pathology; Cancer; Chromosome Deletion; Chromosomes, Artificial, Bacterial; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 10; Chromosomes, Human, Pair 19; Chromosomes, Human, Pair 7; Chromosomes, Human, Pair 9; Disease-Free Survival; Female; Genetics; genomic; Glioma; Glioma - classification; Glioma - genetics; Glioma - pathology; gliomas; group; Humans; Investigative techniques, diagnostic techniques (general aspects); Life Sciences; Loss of Heterozygosity; Male; Medical sciences; Middle Aged; Multivariate Analysis; Nervous system; Neurons and Cognition; Nucleic Acid Hybridization; Oligodendroglioma; Oligodendroglioma - genetics; Oligodendroglioma - pathology; Oligonucleotides; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Receptor, Epidermal Growth Factor; Receptor, Epidermal Growth Factor - genetics; Survival Analysis; Tumors; World Health Organization; Human; Nervous system diseases; Prognosis; BAC array CGH; BAC array; Malignant tumor; Malignant glioma; Cancerology; Comparative genomic hybridization; genomic; Central nervous system disease; Genetics; Molecular biology; Genome; gliomas; Subtype; Cancer; group
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.23270

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.