1. ¹Department of Pathology, Division of Molecular Histopathology, University of Cambridge, Cambridge, UK
2. ²Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
3. ³The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK
4. ⁴Duke Center for Human Genetics, Duke University Medical Center, Durham, NC, USA

Correspondence: Dr K Ichimura, Department of Pathology, Division of Molecular Histopathology, University of Cambridge, Level 3, Lab Block, Addenbrooke's Hospital, Box 231, Cambridge CB2 0QQ, UK. E-mail: ki212@cam.ac.uk

Received 16 July 2007; Revised 5 September 2007; Accepted 17 September 2007; Published online 15 October 2007.

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.