Genetic and epigenetic analysis of the TIMP-3 gene in ovarian cancer.

Chromosome 22q shows a high frequency of loss of heterozygosity (LOH) in ovarian cancers suggesting the existence of one or more important tumor suppressor genes (TSGs). The tissue inhibitor of metalloproteinase-3 (TIMP-3) is a plausible TSG candidate since it is often encompassed within these regions of LOH. TIMP-3 has not previously been investigated for somatic mutations or promoter hypermethylation in ovarian cancer. We analyzed 65 ovarian cancers for both somatic genetic mutations and TIMP-3 promoter hypermethylation. Screening of all coding exons of TIMP-3 did not reveal any somatic genetic mutations and only 1/65 showed TIMP-3 methylation. Our data indicate that inactivation of TIMP-3 by somatic mutation or promoter hypermethylation is rare in ovarian cancer.