Clinical relevance of SKP2 alterations in metastatic melanoma

Amy E. Rose, Guimin Wang, Douglas Hanniford, Stefano Monni, Ting Tu, Richard L. Shapiro, Russell S. Berman, Anna C. Pavlick, Michele Pagano, Farbod Darvishian, Madhu Mazumdar, Eva Hernando, Iman Osman

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

In this study, we investigated the mechanism(s) of altered expression of protooncogene SKP2 in metastatic melanoma and its clinical relevance in patients with metastatic melanoma. The genomic status of SKP2 was assessed in cell lines by sequencing, single nucleotide polymorphism array, and genomic PCR. Copy number status was then evaluated for concordance with SKP2 mRNA and protein expression. SKP2 protein was further evaluated by immunohistochemistry in 93 human metastatic tissues. No mutations were identified in SKP2. Increased copy number at the SKP2 locus was observed in 6/14 (43%) metastatic cell lines and in 9/22 (41%) human metastatic tissues which was associated with overexpression of SKP2 protein. Overexpression of SKP2 protein in human tissues was associated with worse survival in a multivariate model controlling for the site of metastasis. Copy number gain is a major contributing mechanism of SKP2 overexpression in metastatic melanoma. Results may have implications for the development of therapeutics that target SKP2.

Original languageEnglish
Pages (from-to)197-206
Number of pages10
JournalPigment Cell and Melanoma Research
Volume24
Issue number1
DOIs
StatePublished - Feb 2011
Externally publishedYes

Keywords

  • Gene expression
  • Melanoma
  • Metastasis
  • SKP2
  • SNP array

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