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

Handoko, Herlina Y., Boyle, Glen M., Ferguson, Blake, Muller, H. Konrad, Soyer, H. Peter and Walker, Graeme J. (2013) Plasticity of melanoma in vivo: murine lesions resulting from Trp53, but not Cdk4 or Arf deregulation, display neural transdifferentiation. Pigment Cell & Melanoma Research, 26 5: 731-734. doi:10.1111/pcmr.12124


Author Handoko, Herlina Y.
Boyle, Glen M.
Ferguson, Blake
Muller, H. Konrad
Soyer, H. Peter
Walker, Graeme J.
Title Plasticity of melanoma in vivo: murine lesions resulting from Trp53, but not Cdk4 or Arf deregulation, display neural transdifferentiation
Journal name Pigment Cell & Melanoma Research   Check publisher's open access policy
ISSN 1755-1471
1755-148X
Publication date 2013-09-01
Year available 2013
Sub-type Article (original research)
DOI 10.1111/pcmr.12124
Volume 26
Issue 5
Start page 731
End page 734
Total pages 4
Place of publication Malden, United States
Publisher Wiley-Blackwell Publishing
Language eng
Formatted abstract
We previously noted that melanomas developing in Cdk4R24C/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.
Keyword melanoma
mice
transdifferentiation
Trp53
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
 
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