Chromosome 22 tiling-path array-CGH analysis identifies germ-line- and tumor-specific aberrations in patients with glioblastoma multiforme

Diaz de Stahl, T., Hartmann, C., de Bustos, C., Piotrowski, A., Benetkiewicz, M., Mantripragada, Kiran Kumar ORCID: https://orcid.org/0000-0003-2070-8105, Tykwinski, T., von Deimling, A. and Dumanski, J. P. 2005. Chromosome 22 tiling-path array-CGH analysis identifies germ-line- and tumor-specific aberrations in patients with glioblastoma multiforme. Genes, Chromosomes and Cancer 44 (2) , pp. 161-169. 10.1002/gcc.20226

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Abstract

Gliomas are common and frequently malignant tumors of the central nervous system. Recurrent allelic losses of chromosome 22 have been reported in gliomas, indicating tumor-suppressor genes at this location. However, the target genes are still unknown. We applied a high resolution tiling-path chromosome 22 array to a series of 50 glioblastoma samples, with the aim of investigating the underlying abnormalities in both constitutional and tumor-derived DNA. We detected hemizygous deletions in 28% of the tumors (14 of 50), with monosomy 22 (10 of 50) being the predominant pattern. The distribution of overlapping hemizygous deletions delineated two putative tumor-suppressor loci (11.1 and 3.08 Mb in size) across 22q. Most strikingly, we identified two distinct loci affected by regional gains. Both alterations were of germ-line origin and were unique to samples from patients affected with tumors. Analysis of these two amplified regions revealed the presence of two interesting candidate genes: TOP3B and TAFA5. The TOP3B gene encodes a protein that seems to function in the unlinking of parental strands at the final stage of DNA replication and/or in the dissociation of structures in mitotic cells that could lead to recombination. The TAFA5 gene belongs to a novel family of proteins with similarity to chemokines and brain-specific expression. The role of the identified candidate loci should be studied further. Our results demonstrated the power of array-CGH to determine DNA copy number alterations in the context of germ-line- and tumor-specific aberrations.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects:	R Medicine > R Medicine (General)
Publisher:	Wiley-Liss Inc
ISSN:	1045-2257
Last Modified:	31 Oct 2022 10:02
URI:	https://orca.cardiff.ac.uk/id/eprint/83370

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