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

• Main Authors: Ahmed Idbaih, François Ducray, Caroline Dehais, Célia Courdy, Catherine Carpentier, Simon de Bernard, Emmanuelle Uro-Coste, Karima Mokhtari, Anne Jouvet, Jérôme Honnorat, Olivier Chinot, Carole Ramirez, Patrick Beauchesne, Alexandra Benouaich-Amiel, Joël Godard, Sandrine Eimer, Fabrice Parker, Emmanuelle Lechapt-Zalcman, Philippe Colin, Delphine Loussouarn, Thierry Faillot, Phong Dam-Hieu, Selma Elouadhani-Hamdi, Luc Bauchet, Olivier Langlois, Caroline Le Guerinel, Denys Fontaine, Elodie Vauleon, Philippe Menei, Marie Janette Motsuo Fotso, Christine Desenclos, Pierre Verrelle, François Ghiringhelli, Georges Noel, François Labrousse, Antoine Carpentier, Frédéric Dhermain, Jean-Yves Delattre, Dominique Figarella-Branger, POLA Network
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2012-01-01
• Series: PLoS ONE
• Online Access: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23071531/pdf/?tool=EBI

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.