Loss of heterozygosity in human ovarian cancer on chromosome 19q.

Abnormalities in the function of oncogenes and tumor suppressor genes have been associated with many human malignancies. The recognition of sites of loss of heterozygosity (LOH) has led to the identification of such genes. We previously reported that abnormalities of mRNA expression of ERCC1 and ERCC2 may be characteristic of epithelial ovarian carcinoma and brain tumors. This led to an investigation of chromosome 19q13.2-q13.4 which contains these DNA repair genes. A 7-Mb region was analyzed using six microsatellite repeats. Loss of heterozygosity has been identified in 53% (8/15) of cases at marker D19S246 which lies in a 2-Mb segment between HRC and KLK1. The genetic material both centromeric and telomeric to the region of loss was conserved. This area is telomeric to three DNA repair genes where LIG1 is 1-Mb centromeric and ERCC1 and ERCC2 are 3.5- and 4.0-Mb centromeric, respectively. These findings represent the first report of a biologically significant rate of LOH on chromosome 19q13.2-q13.4 in human ovarian carcinoma.