Isolation and characterization of glioblastoma-associated homozygously deleted DNA fragments from chromosomal region 9p21 suggests involvement of multiple tumour suppressor genes.
Representational difference analysis (RDA) of a human glioblastoma xenograft resulted in the isolation of five tumour-associated homozygously deleted DNA fragments, all originating from chromosome 9, region p21. Subsequent analysis of a series of ten glioblastomas using the newly isolated RDA fragments in conjunction with a series of known 9p21 DNA markers revealed homozygous deletions in nine of the ten (90 per cent) tumours. These deletions encompass the p15/p16 complex and two additional putative tumour suppressor loci. The RDA fragments correspond to the latter two loci. Taken together, these results suggest the involvement of multiple tumour suppressor genes from the 9p21 region in glioblastoma tumourigenesis. The novel RDA fragments will be instrumental in the isolation of the relevant genes.
Simons
A
A
Department of Human Genetics, University Hospital Nijmegen, The Netherlands. A.Simons@antrg.azn.nl
Jeuken
J W
JW
Eleveld
M J
MJ
Boerman
R H
RH
Geurts Van Kessel
A
A
D000818:Animals; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers; D005909:Glioblastoma / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D009368:Neoplasm Transplantation; D016133:Polymerase Chain Reaction / Q000379:methods; D014183:Transplantation, Heterologous
D004273:DNA, Neoplasm; D005819:Genetic Markers