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

ABSTRACT: 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.

SUBMITTER: Idbaih A

PROVIDER: S-EPMC3468603 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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

Idbaih Ahmed A Ducray François F Dehais Caroline C Courdy Célia C Carpentier Catherine C de Bernard Simon S Uro-Coste Emmanuelle E Mokhtari Karima K Jouvet Anne A Honnorat Jérôme J Chinot Olivier O Ramirez Carole C Beauchesne Patrick P Benouaich-Amiel Alexandra A Godard Joël J Eimer Sandrine S Parker Fabrice F Lechapt-Zalcman Emmanuelle E Colin Philippe P Loussouarn Delphine D Faillot Thierry T Dam-Hieu Phong P Elouadhani-Hamdi Selma S Bauchet Luc L Langlois Olivier O Le Guerinel Caroline C Fontaine Denys D Vauleon Elodie E Menei Philippe P Fotso Marie Janette Motsuo MJ Desenclos Christine C Verrelle Pierre P Ghiringhelli François F Noel Georges G Labrousse François F Carpentier Antoine A Dhermain Frédéric F Delattre Jean-Yves JY Figarella-Branger Dominique D

PloS one 20121010 10

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 ...[more]

PMID: 23071531

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Project description:Background: Insufficient quantities of human genomic DNA are a limiting factor for many clinical applications. Whole genome amplification (WGA) is an approach designed to overcome small amount of DNA for genome-wide genetic tests as it allows amplification of the entire genome from picogram or nanogram quantities of DNA. Various strategies of WGA have been developed; however, none of them can guarantee the absence of amplification bias. High-quality genome-representative amplified DNA is crucial for WGA use in basic research and clinical genetics. Thus, systematic evaluation of WGA effect on downstream methods is necessary. Results: In this paper, 4 multiple displacement amplification (MDA) -based and 2 PCR-based WGA kits were compared in their effect on segmental copy-number changes as well as copy-number neutral loss of heterozygosity detection by high-density oligonucleotide DNA arrays. We described outcomes and limits for each individual WGA; however, the main goal of this study was chiefly to show a general compatibility and features specific for particular WGA strategy. The main outcomes are as follows: 1) MDA-based WGAs showed higher tendency to generate false positive imbalances in contrast to PCR-based WGAs with higher risk of false negativity; 2) the specific risk of false positivity and/or negativity increased with decreasing copy-number segments size; 3) single-cell WGAs showed significantly worse effect on results in comparison to WGAs with nanogram level of DNA as input; 4) PCR-based WGAs were not compatible with copy-number neutral loss of heterozygosity analysis based on single nucleotide polymorphisms in restriction digestion sites and also showed higher risk of copy-number neutral loss of heterozygosity false negativity if combined with analysis based on simple hybridization. Conclusions: This study gives a comprehensive insight into the WGA effect on DNA array analysis. The results of this study help to choose WGA according to individual user requirements and options. Moreover, we show a strategy to verify and validate segmental copy-number changes detection by DNA array protocol including any WGA for any purpose to attain the highest efficiency without an unnecessary WGA bias.

Dataset Information

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

Publications

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

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