Genetic instability leads to loss of both p53 alleles in a human glioblastoma

Abstract

Little is known about the relationship between genetic recombination mechanisms and loss of tumour suppressor genes in solid tumours. Here, we demonstrate deletion and truncation of both p53 alleles in a primary human glioblastoma and a derived cell line as the combined result of a t(17;20) reciprocal translocation and a 1.1 Mbp genomic deletion on chromosome 17p, starting in intron 4 of the p53 gene and ending at the telomeric CA-repeat marker D17S960. These results (i) suggest that genetic instability can lead to loss of tumour suppressor gene function in solid cancers, (ii) provide mapping of one such recombination event at the nucleotide level, and (iii) establish the orientation of the p53 gene on chromosome 17 as: centromere 5'-3'-telomere.