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Plasticity of melanoma in vivo: murine lesions resulting from Trp53, but not Cdk4 or Arf deregulation, display neural transdifferentiation
Author(s) -
Handoko Herlina Y.,
Boyle Glen M.,
Ferguson Blake,
Muller H. Konrad,
Soyer H. Peter,
Walker Graeme J.
Publication year - 2013
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12124
Subject(s) - microphthalmia associated transcription factor , neuroblastoma ras viral oncogene homolog , biology , neural crest , melanocyte , melanoma , cancer research , microbiology and biotechnology , gene , genetics , mutation , transcription factor , kras
Summary 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 .