Abstract
The human androgen receptor gene contains a polymorphic CAG repeat
region ranging from 8 to about 35 repeats in the normal human population.
The repeat length is inversely related to the transactivation potential
of the receptor. We have analyzed the repeat length in 50 sporadic
colon cancer samples in comparison to surrounding healthy mucosa
and have found somatic reductions of up to 10 repeats in 5 cases
(10%), 3 of which were complex, probably involving both alleles.
Alterations occurred in tumors with and without microsatellite instability
indicating that they follow an independent mutation pathway. The
similar repeat of the huntingtin gene did not show any somatic alterations
in the same cases. No correlation to sex, tumor stage, location,
or histology was evident. In the tumors that showed somatic reductions,
the reduced allele was present in at least half of the cells and
thus in most, if not all, of the tumor component of the sample. Somatic
reductions of the androgen receptor CAG repeat thus occur frequently,
through a pathway distinct from microsatellite instability and early
during colon carcinogenesis. The receptor is expressed in most normal
and neoplastic tissue samples analyzed. Apparent growth selection
of cells bearing shortened AR alleles suggests that androgens contribute
to colon carcinogenesis in a yet unknown way.
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