ANDROGEN RECEPTOR GENE-MUTATIONS IN HUMAN PROSTATE-CANCER

To investigate the structural abnormality of the androgen receptor (AR ) in human prostate cancers, exons B-H encoding DNA- and hormone-bindi ng domains were examined by single-strand conformation polymorphism an alysis of polymerase chain reaction products using originally designed oligoprimers. Tissues from 7 cases of untreated stage B prostate canc er surgically removed and from 8 cases of endocrine therapy-resistant cancers obtained at autopsy were used in the study. Two different muta tions were identified in exons D and H in the different cancer foci of the same cancer death patient. One mutation in exon D (at codon 701, Leu to His) was detected in the prostate, and the other in exon H (at codon 877, Thr to Ala) was found in metastatic tissues. In untreated c ancer tissues and the other autopsy samples, no mutations were detecte d. The mutation in exon H was identical to that reported in LNCaP cell s. These results indicate that AR gene mutations occur in relation to endocrine therapy-resistance, although the mutation was found in 1 out of 8 resistant cases (12.5%) at autopsy.