SNP array analysis reveals novel genomic abnormalities including copy neutral loss of heterozygosity in anaplastic oligodendrogliomas

• Published in: PloS one Vol. 7; no. 10; p. e45950
• Main Authors: Idbaih, Ahmed, Ducray, François, Dehais, Caroline, Courdy, Célia, Carpentier, Catherine, de Bernard, Simon, Uro-Coste, Emmanuelle, Mokhtari, Karima, Jouvet, Anne, Honnorat, Jérôme, Chinot, Olivier, Ramirez, Carole, Beauchesne, Patrick, Benouaich-Amiel, Alexandra, Godard, Joël, Eimer, Sandrine, Parker, Fabrice, Lechapt-Zalcman, Emmanuelle, Colin, Philippe, Loussouarn, Delphine, Faillot, Thierry, Dam-Hieu, Phong, Elouadhani-Hamdi, Selma, Bauchet, Luc, Langlois, Olivier, Le Guerinel, Caroline, Fontaine, Denys, Vauleon, Elodie, Menei, Philippe, Fotso, Marie Janette Motsuo, Desenclos, Christine, Verrelle, Pierre, Verelle, Pierre, Ghiringhelli, François, Noel, Georges, Labrousse, François, Carpentier, Antoine, Dhermain, Frédéric, Delattre, Jean-Yves, Figarella-Branger, Dominique
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10-10-2012; Public Library of Science (PLoS)
• Subjects: Abnormalities; Adult; Adults; Aged; Bioinformatics; Biological materials; Biology; Blood banks; Brain cancer; Brain Neoplasms; Brain Neoplasms - genetics; Brain research; Cellular Biology; Chromosome deletion; Dehydrogenases; DNA methylation; Female; Gene amplification; Gene Deletion; Gene expression; Genes; Genes, p16; Genes, p16 - physiology; Heterozygosity; Humans; Life Sciences; Loss of Heterozygosity; Male; Medical diagnosis; Medical prognosis; Medicine; Middle Aged; Mutation; Neurosciences; Oligodendroglioma; Oligodendroglioma - genetics; Patients; Polymorphism; Polymorphism, Single Nucleotide; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Subgroups; Tumor suppressor genes; Tumors; France
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0045950

Anaplastic oligodendrogliomas (AOD) are rare glial tumors in adults with relative homogeneous clinical, radiological and histological features at the time of diagnosis but dramatically various clinical courses. Studies have identified several molecular abnormalities with clinical or biological relevance to AOD (e.g. t(1;19)(q10;p10), IDH1, IDH2, CIC and FUBP1 mutations).To better characterize the clinical and biological behavior of this tumor type, the creation of a national multicentric network, named "Prise en charge des OLigodendrogliomes Anaplasiques (POLA)," has been supported by the Institut National du Cancer (InCA). Newly diagnosed and centrally validated AOD patients and their related biological material (tumor and blood samples) were prospectively included in the POLA clinical database and tissue bank, respectively.At the molecular level, we have conducted a high-resolution single nucleotide polymorphism array analysis, which included 83 patients. Despite a careful central pathological review, AOD have been found to exhibit heterogeneous genomic features. A total of 82% of the tumors exhibited a 1p/19q-co-deletion, while 18% harbor a distinct chromosome pattern. Novel focal abnormalities, including homozygously deleted, amplified and disrupted regions, have been identified. Recurring copy neutral losses of heterozygosity (CNLOH) inducing the modulation of gene expression have also been discovered. CNLOH in the CDKN2A locus was associated with protein silencing in 1/3 of the cases. In addition, FUBP1 homozygous deletion was detected in one case suggesting a putative tumor suppressor role of FUBP1 in AOD.Our study showed that the genomic and pathological analyses of AOD are synergistic in detecting relevant clinical and biological subgroups of AOD.