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 hyperplasia and has been suggested to prevent prostate cancer development. To gain insight to the molecular effects of finasteride on prostate cancer development, we studied six prostate cancers diagnosed during finasteride treatment for benign prostatic hyperplasia. Comparative genomic hybridization detected genetic alterations in four tumors (1-5 changes/tumor). Xq gains and 6q losses were the most common alterations. The recurrent Xq gains motivated us to study the involvement of the androgen receptor (AR) gene. One tumor with 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 recurring during hormonal therapy. Furthermore, in another tumor, an Arg726Leu 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 reported to affect the transactivational properties of the AR. In summary, prostate cancers developing during finasteride therapy may have distinct biological properties, such as a low number of chromosomal alterations and frequent involvement of the AR gene. Further studies are needed to explore the role of germ-line AR mutations in these patients.
Koivisto
P A
PA
Laboratory of Cancer Genetics, Tampere University Hospital, Finland. blpako@uta.fi
Schleutker
J
J
Helin
H
H
Ehren-van Eekelen
C
C
Kallioniemi
O P
OP
Trapman
J
J
D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D018120:Finasteride / Q000627:therapeutic use*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009367:Neoplasm Staging; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011944:Receptors, Androgen / Q000235:genetics*; D014960:X Chromosome
D004791:Enzyme Inhibitors; D011944:Receptors, Androgen; D018120:Finasteride