Ultraviolet B-induced melanoma in Monodelphis domestica occurs in the absence of alterations in the structure or expression of the p53 gene

Monodelphis domestica, a South American opossum, has been established as a mammalian model for sporadic ultraviolet radiation (UVR)-induced melanoma. Using this model system, we investigated the role of changes in the p53 gen e in the development of cutaneous melanocyte-derived lesions. Cutaneous mel anocytic hyperplasias, benign melanomas and metastatic primary melanomas, p lus affected lymph nodes and visceral organs, were screened for mutations i n the Monodelphis p53 gene by single-strand conformation polymorphism analy sis and direct sequencing. With the exception of a silent point mutation fo und in a single benign melanocytic hyperplasia sample, no p53 mutations wer e detected. Furthermore, a relative quantitative reverse transcriptase-poly merase chain reaction approach was used to analyse p53 gene expression at d ifferent stages of primary melanoma progression and revealed no substantial changes in p53 mRNA levels. These results suggest that, as in humans, UVR- induced melanoma in the Monodelphis model is initiated and progresses on th e basis of predominantly p53-independent molecular pathways. (C) 2001 Lippi ncott Williams & Wilkins.