1. Plasticity of melanoma in vivo: murine lesions resulting from Trp53, but not Cdk4 or Arf deregulation, display neural transdifferentiation.
- Author
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Handoko, Herlina Y., Boyle, Glen M., Ferguson, Blake, Muller, H. Konrad, Soyer, H. Peter, and Walker, Graeme J.
- Subjects
MELANOMA ,GENETIC regulation ,GENETIC polymorphisms ,EPITHELIAL cells ,ESOPHAGEAL cancer - Abstract
We previously noted that melanomas developing in Cdk4
R24C/R24C ::Tyr- NRAS, Arf−/− ::Tyr- NRAS and Trp53F/F ::Tyr-Cre( ER)::Tyr- NRAS mice exhibited differences in behaviour in vivo. We investigated this phenomenon using global gene expression profiling of lesions from the respective genotypes. While those from the Cdk4- and Arf-mutant mice exhibited similar profiles, the Trp53F/F ::Tyr-Cre( ER)::Tyr- NRAS melanomas were strikingly different, showing relative down-regulation of melanocyte-related genes, and up-regulation of genes related to neural differentiation. Specifically, they highly expressed genes representative of the myelin-producing peripheral oligodendrite (Schwann cell) lineage, although histopathologically the lesions did not exhibit the classical features of schwannoma. As Schwann cell precursors can be a cellular origin of melanocytes, it is unsurprising that plasticity with respect to melanocyte-neural differentiation can occur in melanoma. What is surprising is the genotype proclivity. Comparison of gene expression signatures revealed that melanomas from the Trp53-mutant mice show significant similarities with a subset of aggressive human melanomas with relatively low levels of MITF. [ABSTRACT FROM AUTHOR]- Published
- 2013
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