Return to article

Exon Position Change codon/amino acid Characteristics Ref. 4 720 GCCACC AT Isolated from a hormone refractory bone marrow metastasis from a patient treated with flutamide and an LHRH agonist. Does not become transcriptionally active in response to estradiol or progesterone. Shows moderate transcriptional activation in response to 1 µM nilutamide, but not HF or bicalutamide. Demonstrates a reduced response to DHT in vitro compared to the wild-type receptor. 152 336 341 5 725 CGCCTC RL Germline mutation observed in 2% of Finnish sporadic prostate cancer patients. The AR CAG repeat length is 26 in 85% of mutation carriers. This mutation does not alter the ability of the mutant AR to bind mibolerone, DHT, estradiol, or progesterone. However, this mutation enhances AR transcription in response to estradiol compared to the wild-type receptor in CV-1 cells. This mutation also can be activated by DHEA in vitro. 152 342 411 5 729 GTGATG VM Isolated from a patient with organ-confined prostate cancer who had not received hormonal therapy. This mutant shows enhanced transactivation in response to HF, androsterone, and androstanediol. However, the relative binding affinity of the mutant receptor for R1881, androstenediol, androstanediol, and androsterone is the same as the wild-type receptor. 409 412 5 740 TGGTAG WStop Detected in an archival latent prostatic tumor sample from a Japanese man. 327 5 740 TGGTGT WC Identified from a TURP sample from a hormone refractory tumor treated with a combination of orchiectomy and bicalutamide. The same amino acid substitution has also been isolated from a bone marrow metastasis from a patient with hormone refractory cancer after treatment with bicalutamide. 406 407 5 742 GGGGGC GG Stop Deletion causing a frameshift mutation resulting in a stop codon after 1 amino acid. Detected in an archival latent prostatic tumor sample from a Japanese man. A separate latent tumor foci in the same individual contained the L743F mutation. 327 5 743 CTCTTC LF Detected in an archival latent prostatic tumor sample from a Japanese man. A separate latent tumor foci from the same individual contained the 742 mutation. 327 5 747 GGCGTC AV Detected in an archival latent prostatic tumor sample from a Japanese man. This mutation results in a decreased transcriptional response to DHT compared to the wild-type receptor in vitro. Can also be transcriptionally activated by DHEA in vitro. 152 327 5 748 ATGATA MI Detected in an archival latent prostatic tumor sample from a Japanese man. This mutant does not become transcriptionally active in vitro in response to DHT, DHEA, progesterone, estradiol, hydrocortisone, flutamide, or bicalutamide. 152 327 5 748 ATGATA MI Isolated from a TURP sample from a hormone refractory tumor after treatment by orchiectomy and bicalutamide. 406 5 749 GGCAGC GS Detected in an archival latent prostatic tumor sample from a Japanese man. This mutant can be transcriptionally activated in vitro by DHEA. 152 327 5 750 TGGTAG WStop Detected in two archival latent prostatic tumor samples from Japanese men. 327 5 754 ACCGCC TA Detected in an archival latent prostatic tumor sample from a Japanese man. 327 5 756 GTCGCC VA Isolated from a pelvic lymph node metastasis. The mutant receptor can be transcriptionally activated by DHEA in vitro. 152 328 5 758 TCCCCC SP Detected in an archival latent prostatic tumor sample from a Japanese man. This mutant shows a reduced transcriptional activity in response to DHT in vitro compared to the wild-type receptor. 152 327 5 762 TACTGC YC Detected in an archival latent prostatic tumor sample from a Japanese man. This mutant become transcriptionally active in vitro in response to DHT but not estradiol, DHEA, progesterone, hydrocortisone, flutamide, or bicalutamide. 152 327 6 781 AGCAAC SN Isolated from a TURP sample prior to hormonal therapy. The mutant can be transcriptionally activated by DHT and DHEA in vitro. 152 330 6 795 TGGTGA WSTOP Isolated from a TURP sample prior to hormonal therapy. 330 7 845 AGAGGA RG Isolated from a pelvic lymph node metastasis. This mutation can show transcriptional activation in vitro in response to DHT and DHEA. 152 328 8 865 GTGATG VM Detected in an archival latent prostatic tumor sample from a Japanese man. This mutation fails to be activated by DHT, DHEA, estradiol, progesterone, hydrocortisone, flutamide, or bicalutamide in vitro. 152 327

Continued on next page

Return to article