Cancer is known to be a
genetic disease that is both polygenic and heterogeneous, in most cases involving changes in several genes in a stepwise fashion. The spectrum of individual genes involved in the initiation and progression of
cancer is greatly influenced by genetic factors unique to each patient. A study of complex diseases such as
cancer is complicated by the genetic heterogeneous background and environmental factors in the human population.
Endometrial cancer (EC) is ranked fourth among invasive
tumors in women. In Sweden, approximately 1300 women (27/100,000 women) are diagnosed annually. To be able to study the genetic alterations in
cancer, the use of an animal model is very convenient. Females of the BDII strain are genetically predisposed to EC and 90% of female BDII rats develop EC during their lifetime. Thus, BDII rats have been used to model human EC with respect to the genetics of susceptibility and of
tumor development. A set of rat EC
tumors was analyzed using conventional cytogenetics and comparative genome hybridization (CGH).
Chromosomal aberrations, i.e., gains, were found on rat chromosome 4 (RNO4). Using FISH analysis, we concluded that the Met oncogene and Cdk6 (
cyclin-dependent kinase 6) were amplified in this set of EC
tumors. The data from this investigation were used to analyze a set of human endometrial
tumors for amplification of Cdk6 and Met. Our preliminary data are indicative for a good correlation between our findings in the BDII rat model for EAC and the situation in human EC. These data provide strong support for the use of animal model systems for better understanding and scrutinizing of human complex disease of
cancer.