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-Subunit Gene in Prostate Carcinoma
Monash Institute of Reproduction and Development (J.F.S., M.F., G.P.R.), Monash University, Clayton, Victoria 3168, Australia; Kanematsu Laboratories (D.S.M., J.S.P., S.L.C., G.P.R.), Royal Prince Alfred Hospital, Camperdown, New South Wales 2050; Melbourne Pathology (J.S.P.), Collingwood, Victoria 3066; Peter MacCallum Cancer Institute (D.J.V.), Melbourne 3002; and CSIRO Molecular Science (P.L.M.), North Ryde, New South Wales 1670, Australia
Address all correspondence and requests for reprints to: Dr. Gail P. Risbridger, Monash Institute of Reproduction and Development, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria 3168, Australia.
Inhibin is composed of an 
- and a ß-subunit. Transgenic
studies assigned a tumor-suppressive role to the inhibin -subunit,
and in human prostate cancer inhibin -subunit gene expression was
down-regulated. This study examined the inhibin -subunit gene
promoter and gene locus to determine whether promoter hypermethylation
or LOH occurred in DNA from prostate cancer. The 5'-untranslated region
of the human inhibin -subunit gene was sequenced and shown to be
highly homologous to the bovine, rat, and mouse inhibin -subunit
promoter sequences. A 135-bp region of the human promoter sequence that
continued a cluster of CpG sites was analyzed for hypermethylation.
Significant (P < 0.001) hypermethylation of the
inhibin -subunit gene promoter occurred in DNA from Gleason pattern
3, 4, and 5 carcinomas compared with nonmalignant tissue samples. A
subset of the carcinomas with a cribriform pattern were unmethylated.
LOH at 2q32–36, the chromosomal region harboring the inhibin
-subunit gene, was observed in 42% of prostate carcinomas. These
data provide the first demonstration that promoter hypermethylation and
LOH are associated with the inhibin -subunit gene and gene locus in
prostate cancer.
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