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Pigment Cell Melanoma Res. 2013 Sep;26(5):731-4. doi: 10.1111/pcmr.12124. Epub 2013 Jun 20.

Plasticity of melanoma in vivo: murine lesions resulting from Trp53, but not Cdk4 or Arf deregulation, display neural transdifferentiation.

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1
Queensland Institute of Medical Research, Herston, Qld, Australia.

Abstract

We previously noted that melanomas developing in Cdk4(R24C/R24C) ::Tyr-NRAS, Arf(-/-) ::Tyr-NRAS and Trp53(F/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 Trp53(F/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.

KEYWORDS:

Trp53; melanoma; mice; transdifferentiation

PMID:
23724991
DOI:
10.1111/pcmr.12124
[Indexed for MEDLINE]
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