title: Chromosome 22 tiling-path array-CGH analysis identifies germ-line- and tumor-specific aberrations in patients with glioblastoma multiforme.
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.
authors.affiliation: Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Teresita
authors.initials: T
authors.lastname: Díaz de Ståhl
authors.forename: Christian
authors.initials: C
authors.lastname: Hartmann
authors.forename: Cecilia
authors.initials: C
authors.lastname: de Bustos
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Piotrowski
authors.forename: Magdalena
authors.initials: M
authors.lastname: Benetkiewicz
authors.forename: Kiran K
authors.initials: KK
authors.lastname: Mantripragada
authors.forename: Tomasz
authors.initials: T
authors.lastname: Tykwinski
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
authors.forename: Jan P
authors.initials: JP
authors.lastname: Dumanski
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22; D020022:Genetic Predisposition to Disease; D005854:Germ Cells; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D009693:Nucleic Acid Hybridization