SNP array analysis reveals novel genomic abnormalities including copy neutral loss of heterozygosity in anaplastic oligodendrogliomas.
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.
Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière (CRICM), UMRS 975, Paris, France. ahmed.idbaih@gmail.com
Ahmed
A
Idbaih
François
F
Ducray
Caroline
C
Dehais
Célia
C
Courdy
Catherine
C
Carpentier
Simon
S
de Bernard
Emmanuelle
E
Uro-Coste
Karima
K
Mokhtari
Anne
A
Jouvet
Jérôme
J
Honnorat
Olivier
O
Chinot
Carole
C
Ramirez
Patrick
P
Beauchesne
Alexandra
A
Benouaich-Amiel
Joël
J
Godard
Sandrine
S
Eimer
Fabrice
F
Parker
Emmanuelle
E
Lechapt-Zalcman
Philippe
P
Colin
Delphine
D
Loussouarn
Thierry
T
Faillot
Phong
P
Dam-Hieu
Selma
S
Elouadhani-Hamdi
Luc
L
Bauchet
Olivier
O
Langlois
Caroline
C
Le Guerinel
Denys
D
Fontaine
Elodie
E
Vauleon
Philippe
P
Menei
Marie Janette Motsuo
MJ
Fotso
Christine
C
Desenclos
Pierre
P
Verrelle
Pierre
P
Verelle
François
F
Ghiringhelli
Georges
G
Noel
François
F
Labrousse
Antoine
A
Carpentier
Frédéric
F
Dhermain
Jean-Yves
JY
Delattre
Dominique
D
Figarella-Branger
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D019942:Genes, p16 / Q000502:physiology; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009837:Oligodendroglioma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide