p53 tumour suppressor gene mutations in benign prostatic hyperplasia and prostate cancer.

Abstract

To identify and analyse point mutations in p53 tumour suppressor gene (Tp53) in benign prostatic hyperplasia (BPH) by temperature gradient gel electrophoresis (TGGE) and sequence. 141 tissue specimens (approx. 100 mg) after transurethral resection of the prostate (TURP), 12 specimens after needle biopsy. Control samples for genetic analysis were (a) 7 prostate tissues without any sign of BPH and malignancy and (b) 103 prostate cancer (PCa) tissues. DNA of the critical Tp53 exons 5-8 was amplified and run on horizontal polyacrylamide gels under defined temperature conditions (TGGE) to yield specific gel shifts and sets of homo- and heteroduplexes in case of mutation. Sequencing with a laser-fluorescent electrophoresis unit was done from re-amplified mutant and wild-type bands. TGGE screening of 153 BPH samples identified 29 specimens with Tp53 mutations (5 in exon 5, 11 in exon 6, 12 in exon 7, 3 in exon 8; 1 tissue sample showed mutations in 3 exons at a time). The computed mutation frequency was 19.0%. Two patients, with mutation in BPH tissue, developed PCa 2-3 years after TURP. One patient with mutation in BPH tissue developed bladder cancer. Of 118 patients with non-mutated DNA in BPH, none is known to have a urological cancer. The Tp53 mutation frequency in 103 PCa samples was 26.2%. Significant differences of mutation frequency between BPH and PCa were detected only in lower exon 5 mutation counts in BPH. Tp53 mutation in BPH tissue may be a tumour risk factor.