Microsatellite mutation (CAG_24→18) in the androgen receptor gene in human prostate cancer

The androgen receptor (AR) gene contains a polymorphic CAG microsatellite that codes for a variable length of glutamine repeats in the AR protein. Microsatellite DNA sequences may be potential sites of genetic instability. Using the polymerase chain reaction (PCR), we screened 40 human prostate cancer specimens for expansions or deletions of this microsatellite. In one patient, nontumor DNA yielded a single PCR product, as expected for the AR, but the tumor DNA yielded two discrete products, one identical to normal, and a second smaller one. Direct sequencing revealed that the nontumor tissue contained 24 CAGs, whereas the tumor contained one fragment with 24 CAGs (wild-type) and a second fragment with 18 CAGs (mutant), representing a somatic contraction of the AR CAG repeat (CAG₂₄→CAG₁₈) in the tumor. Interestingly, this patient manifested a paradoxical agonistic response to hormonal therapy with the antiandrogen flutamide.