Mutations in microsatellite sequences, especially expansion in the num
ber of di- and trinucleotide repeats, have been implicated as the caus
e of several heritable disorders, including fragile X syndrome and myo
tonic dystrophy. We examined the possibility that a similar mutation m
echanism might be involved in human prostate cancer. Our findings indi
cate that mutations in microsatellite sequences are frequent in prosta
te cancer. Six of thirty patients (20%) had an allele gain in at least
one microsatellite sequence; three patients (10%) had allele gains in
multiple loci. The new alleles were present in the tumor DNA, but not
in the normal DNA. Although we did not detect mutations in the androg
en receptor microsatellite sequences, it is likely that this type of m
utation affects other genes important in prostate cancer, thereby prom
oting tumor development and progression.