Loss of heterozygosity of the TP53 tumor suppressor gene and detection of point mutations by the non-isotopic RNAse cleavage assay in prostate cancer

Abstract

Mutation within the TP53 tumor suppressor gene is a frequent occurrence in human cancers, resulting in a poor prognosis, response to therapy, and overall survival time. Mutations have been primarily detected in advanced prostate cancer; however, the involvement of the gene through loss of heterozygosity (LOH) in primary prostate cancers has not been investigated due to lack of identifiable polymorphisms within this gene. Using the nonisotopic RNAse cleavage assay (NIRCA), we screened for point mutations and identified an ApaI restriction site polymorphism located in intron 7 within the TP53 gene. This polymorphism allowed us to detect LOH in informative samples in a population of patients that underwent prostate biopsies and a population that underwent radical prostatectomies. Within the combined study population, 31 of 80 patients (38.75%) were informative for the polymorphism. Loss of heterozygosity was detected in 10 of the 31 samples (32.3%). Point mutations were identified in two samples. The identification of LOH in these patients suggests that the TP53 tumor suppressor gene may play a more active role in prostate cancer than was previously believed.