Jp. Gaddipati et al., FREQUENT DETECTION OF CODON-877 MUTATION IN THE ANDROGEN RECEPTOR GENE IN ADVANCED PROSTATE CANCERS, Cancer research, 54(11), 1994, pp. 2861-2864
Prostatic tissue specimens derived from transurethral resections of pa
tients with metastatic prostate cancer were analyzed for genetic alter
ations in the hormone-binding domain of the androgen receptor (AR) gen
e. Direct sequencing of the polymerase chain reaction derived DNAs of
6 of 24 specimens revealed a codon 877 mutation (ACT --> GCT, Thr -->
Ala) in the hormone-binding domain of the AR gene. This same AR mutati
on has been reported previously in a metastatic prostate cancer cell l
ine, LNCaP, where this mutation confers upon the AR an altered ligand-
binding specificity which is stimulated by estrogens, progestagens, an
d antiandrogens. It is possible that analogous to an activated/altered
growth factor receptor oncogene, codon 877 mutant AR with altered lig
and binding may provide a selective growth advantage in the genesis of
a subset of advanced prostate cancer. Although estrogens are used inf
requently, antiandrogens are used increasingly in hormonal therapy for
patients with advanced prostate cancer. The stimulatory effect of the
se therapeutic agents on the codon 877 mutant AR further suggests that
this frequently observed AR mutation may contribute to the treatment
refractory disease.