Androgen receptor gene alterations and chromosomal gains and losses in prostate carcinomas appearing during finasteride treatment for benign prostatic hyperplasia

Finasteride is commonly used for the treatment of benign prostatic hyperpla sia and has been suggested to prevent prostate cancer development. To gain insight to the molecular effects of finasteride on prostate cancer developm ent, me studied six prostate cancers diagnosed during finasteride treatment for benign prostatic hyperplasia. Comparative genomic hybridization detect ed genetic alterations in four tumors (1-5 changes/tumor). Xq gains and 6q losses were the most common alterations. The recurrent Xq gains motivated u s to study the involvement of the androgen receptor (AR) gene. One tumor wi th Xq gain had a 3-fold amplification of the AR gene, suggesting that tumor development in finasteride-treated patients may require increased AR copy number and expression, as has previously been shown. for prostate cancers r ecurring during hormonal therapy. Furthermore, in another tumor, an Arg726L eu mutation of the AR gene was found, This mutation was also present in the germ-line DNA of the patient. Arg726Leu mutation has previously been repor ted to affect the trans-activational properties of the AR, In summary, pros tate cancers developing during finasteride therapy may have distinct biolog ical properties, such as a low number of chromosomal alterations and freque nt involvement of the AR gene. Further studies are needed to explore the ro le of germ-line AR mutations in these patients.