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  • Oncogenomics
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1p36 is a preferential target of chromosome 1 deletions in astrocytic tumours and homozygously deleted in a subset of glioblastomas

Oncogene volume 27, pages 2097–2108 (2008)Cite this article

Abstract

Astrocytic, oligodendroglial and mixed gliomas are the commonest gliomas in adults. They have distinct phenotypes and clinical courses, but as they exist as a continuous histological spectrum, differentiating them can be difficult. Co-deletions of total 1p and 19q are found in the majority of oligodendrogliomas and considered as a diagnostic marker and a prognostic indicator. The 1p status of astrocytomas has not yet been thoroughly examined. Using a chromosome 1 tile path array, we investigated 108 adult astrocytic tumours for copy number alterations. Total 1p deletions were rare (2%), however partial deletions involving 1p36 were frequently identified in anaplastic astrocytomas (22%) and glioblastomas (34%). Multivariate analysis showed that patients with total 1p deletions had significantly longer survival (P=0.005). In nine glioblastomas homozygous deletions at 1p36 were identified. No somatic mutations were found among the five genes located in the homozygously deleted region. However, the CpG island of TNFRSF9 was hypermethylated in 19% of astrocytic tumours and 87% of glioma cell lines. TNFRSF9 expression was upregulated after demethylation of glioma cell lines. Akt3 amplifications were found in four glioblastomas. Our results indicate that 1p deletions are common anaplastic astrocytomas and glioblastomas but are distinct from the 1p abnormalities in oligodendrogliomas.

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Accession codes

Accessions

GenBank/EMBL/DDBJ

Abbreviations

BAC:

bacterial artificial chromosome

CGH:

comparative genomic hybridization

CGI:

CpG island

DGGE:

denaturing gradient gel electrophoresis

MSA:

microsatellite analysis

MSP:

methylation-specific PCR

TSG:

tumour suppressor gene

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Acknowledgements

We thank the Mapping Core, Map Finishing and Microarray Facility groups of the Wellcome Trust Sanger Institute, Hinxton, UK, for initial clone supply and verification, Rachel Cooper for technical assistance in the version 1 chromosome 1 array production, the Centre for Microarray resources in the Department of Pathology, University of Cambridge, for printing of the arrays and Bo Nilsson for his assistance in statistical analysis. This work was supported by Cancer Research UK, The Jacqueline Seroussi Memorial Foundation for Cancer Research, Samantha Dickson Brain Tumour Trust, CAMPOD, the Ludwig Institute for Cancer Research and the Wellcome Trust.

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Authors and Affiliations

  1. Department of Pathology, Division of Molecular Histopathology, University of Cambridge, Cambridge, UK

    K Ichimura, A P Vogazianou, L Liu, D M Pearson, K Plant, K Baird & V P Collins

  2. Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

    L M Bäcklund

  3. The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

    C F Langford & S G Gregory

  4. Duke Center for Human Genetics, Duke University Medical Center, Durham, NC, USA

    S G Gregory

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  1. K Ichimura
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Correspondence to K Ichimura.

Additional information

The raw data for array-CGH can be retrieved from the Gene Expression Omnibus database (http://www.ncbi.nlm.nih.gov/geo/, accession no. GSE7428).

Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Ichimura, K., Vogazianou, A., Liu, L. et al. 1p36 is a preferential target of chromosome 1 deletions in astrocytic tumours and homozygously deleted in a subset of glioblastomas. Oncogene 27, 2097–2108 (2008). https://doi.org/10.1038/sj.onc.1210848

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