Chromosomal and genetic abnormalities in models of epithelial carcinogenesis

Conventional cytogenetic studies complemented with restriction fragment and microsatellite length polymorphism analyses have allowed the identification and better understanding of specific genomic abnormalities occurring in various carcinogenesis models. Studies using the mouse skin carcinogenesis system have provided strong evidence that the trisomization of specific chromosomes is one of the mechanisms occurring in premalignant and malignant cells which select in favor of more aggressive phenotypes. These observations are providing dues to better understand the role and mechanisms of the very common trisomies in human carcinogenesis. Recent studies also suggest that expression of the ribonucleoprotein telomerase is important in skin tumor progression. It was observed that a progressive increase in telomerase activity is possibly associated with the increased level of genomic instability and the phenotypic progression of premalignant tumors. The mouse skin system appears to have potential as a useful in vivo model for testing and development of antitelomerase therapeutic approaches. Striking genetic and chromosomal similarities in mechanisms of tumor progression have been observed among different chemical carcinogenesis models. They are discussed herein as examples of possible common pathways of minor progression. Various mouse mammary tumor models are also described, which provide strong evidence suggesting that the lack of a functional p53 gene appears to be a major culprit in favoring the development of aneuploidy and gross chromosomal aberrations.