SOMATIC MUTATIONS AT THE SRD5A2 LOCUS ENCODING PROSTATIC STEROID 5 alpha-REDUCTASE DURING PROSTATE CANCER PROGRESSION

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Abstract

Prostate cancer is a serious public health problem in many industrialized countries.Androgens appear to play a critical role in its etiology. Specifically, the active androgen in the prostate, dihydrotestosterone (DHT) which is synthesized by the enzyme steroid 5 alpha-reductase from testosterone (T), acts as a mitogen. Hence androgen-deprivation is commonly used during prostate cancer therapy. Two isozymes for steroid 5 alpha-reductase have been reported. The type II enzyme is prostate-specific and encoded by the SRD5A2 gene. We have investigated a polymorphic (TA)n dinucleotide repeat in the 3' UTR (untranslated region) of the SRD5A2 gene in 30 matched samples of constitutional ("germline") DNA from peripheral blood lymphocytes and microdissected, pure tumor DNA. We report here 8 LOH (loss of heterozygosity) events and 9 cases of microsatellite instability at this marker. Therefore, almost 57% of the samples examined showed evidence of somatic mutations at the 3' UTR of the SRD5A2 locus. Our data suggest that the SRD5A2 gene may be involved in prostate cancer progression and that this may have relevance for treatment of the disease.

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