Molecular alterations in human skin tumors

Abstract

Several genetic alterations that perturb normal cellular growth control mechanisms can cause cancers. These include point mutations, deletions, translocations, amplifications and gene rearrangements and occur primarily in two classes of interacting genes, oncogenes and tumor suppressor genes. While mutation or amplification of certain oncogenes can facilitate cell growth and tumor formation (Bishop, 1983, 1991; Hunter, 1991; Land, et al., 1983), loss or mutation of tumor suppressor genes, which normally inhibit these processes, can promote tumor formation (Knudson, 1985; Cavenee, et al., 1989; Marshall, 1991). Human skin tumors display multiple genetic alterations such as Ha-ras gene mutation and LOH, N-ras gene amplification, and mutations in p53 tumor suppressor gene. In most cases, the mutations in ras and p53 genes are localized to pyrimidine-rich sequences, particularly C-C sequences, which indicates that these sites are probably the targets for UV-induced DNA damage and subsequent mutation and transformation. Since UV radiation in sunlight is an environmental carcinogen it is important to understand the molecular mechanisms by which UV radiation induces human skin cancers. In addition, suitable animals models are available for comparative studies and risk assessment. By comparing the various genetic alterations detected in sunlight-induced human skin tumors with those present in UV-induced murine skin tumors, it may be possible to identify the carcinogen-related events that are involved in the multi-step process of carcinogenesis. Studies addressing these issues should provide further insights into the molecular mechanisms of UV carcinogenesis.