High-density marker loss of heterozygosity analysis of rat chromosome 10 in endometrial adenocarcinoma

Endometrial cancer is a disease with serious impact on the human population, but not much is known about genetic factors involved in this complex disease. Female BDII rats are genetically predisposed to spontaneous endometrial carcinoma, and the BDII inbred strain provides an experimental animal model for endometrial carcinoma development. In the present study, BDII females were crossed with males from two nonsusceptible inbred rat strains. Endometrial adenocarcinomas (EACs) developed in a proportion of the F1 and F2 progeny. We screened 18 EAC solid tumors and 9 EAC cell cultures for loss of heterozygosity (LOH) using fluorescent-PCR-based marker allelotyping methodology with 47 microsatellite markers covering the proximal part of rat chromosome 10 (RNO 10). Conclusive evidence was obtained for LOH/deletion involving about 56 cM in the proximal part of RNO 10 in DNA from six out of seven informative tumor cell cultures. Analysis of the solid tumors confirmed the presence of LOH in this part of RNO 10 in 14 of 17 informative tumors. However, from the studies in the solid tumors it appeared that in fact three separate segments in the proximal part of RNO 10 were affected. These three LOH/deletion regions were located approximately in cytogenetic bands 10q11-12, 10q22, and 10q24. (C) 2001 Wiley-Liss, Inc.