MUTATION AND MICROSATELLITE INSTABILITY ANALYSIS OF THE ANDROGEN RECEPTOR GENE IN HUMAN PROSTATE-CANCER

To investigate the mechanism for the development of human prostate can cer, examination was made of structural abnormality of the androgen re ceptor (AR) gene in 29 human prostate cancer. AR gene mutations from e xons A to H were examined by PCR-SSCP and microsatellite instability a nalysis using (CAG)n and (GGN)n polymorphic markers in AR gene exon A. A point mutation was found in the exon D hormone-binding domain of AR leading to substitution of glutamine (GAG) for wild-type arginine (CG G) at codon 629 in 1 (3.4%) hormone-independent stage D2 patient. Micr osatellite instability was detected in 5 of the 27 (18.5%) patients, 1 of 6 (16.7%) hormone-independent stage D2 and 4 of 21 (19.0%) hormone -dependent and non-treated prostate cancer patients. AR mutations may possibly be involved in the transition from androgen-dependent to inde pendent stages during androgen ablation therapy.