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Clinical relevance of SKP2 alterations in metastatic melanoma
Author(s) -
Rose Amy E.,
Wang Guimin,
Hanniford Douglas,
Monni Stefano,
Tu Ting,
Shapiro Richard L.,
Berman Russell S.,
Pavlick Anna C.,
Pagano Michele,
Darvishian Farbod,
Mazumdar Madhu,
Hernando Eva,
Osman Iman
Publication year - 2011
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/j.1755-148x.2010.00784.x
Subject(s) - skp2 , cancer research , melanoma , clinical significance , biology , metastasis , metastatic melanoma , immunohistochemistry , concordance , cancer , pathology , medicine , gene , bioinformatics , immunology , genetics , ubiquitin , ubiquitin ligase
Summary 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.