IDENTIFICATION OF 2 GERMLINE POINT MUTATIONS IN THE 5'UTR OF THE ANDROGEN RECEPTOR GENE IN MEN WITH PROSTATE-CANCER

Purpose: As part of an ongoing study to identify germline mutations an d/or polymorphisms in the androgen receptor (AR) gene which might be a ssociated with prostate cancer, the 5'-untranslated region (5'UTR) of the AR gene was screened in genomic DNA of prostate cancer cases, This region, which is >1kb in length, might modulate AR expression by affe cting transcription and/or translation rates. A life-time exposure to enhanced AR expression, in turn, could potentially predispose to prost ate cancer. Materials and Methods: Genomic DNA samples from 38 prostat e cancer cases were analyzed for mutations in the 5'UTR of the AR gene . Results: Two mutations were identified. One mutation, G2T, is locate d within the AR transcription initiation site 1 (AR-TIS I), and the se cond, C214A, within a GC rich region of the 5'UTR. Conclusions: Althou gh 5'UTR mutations in the AR gene might only rarely occur in men with prostate cancer, the occasional mutation in this area may contribute t o the disease by altering rates of transcription and/or translation of this gene.