title: Clinical relevance of SKP2 alterations in metastatic melanoma.
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.
authors.affiliation: Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, NY, USA.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Rose
authors.forename: Guimin
authors.initials: G
authors.lastname: Wang
authors.forename: Douglas
authors.initials: D
authors.lastname: Hanniford
authors.forename: Stefano
authors.initials: S
authors.lastname: Monni
authors.forename: Ting
authors.initials: T
authors.lastname: Tu
authors.forename: Richard L
authors.initials: RL
authors.lastname: Shapiro
authors.forename: Russell S
authors.initials: RS
authors.lastname: Berman
authors.forename: Anna C
authors.initials: AC
authors.lastname: Pavlick
authors.forename: Michele
authors.initials: M
authors.lastname: Pagano
authors.forename: Farbod
authors.initials: F
authors.lastname: Darvishian
authors.forename: Madhu
authors.initials: M
authors.lastname: Mazumdar
authors.forename: Eva
authors.initials: E
authors.lastname: Hernando
authors.forename: Iman
authors.initials: I
authors.lastname: Osman
mesh_terms: D064200:Cdh1 Proteins; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D005260:Female; D018628:Gene Dosage / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D056426:Genetic Loci / Q000235:genetics; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009711:Nucleotides / Q000235:genetics; D016366:Open Reading Frames / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012008:Recurrence; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics*; D016019:Survival Analysis
chemical_list: D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins; C577584:FZR1 protein, human; D009711:Nucleotides; D044786:S-Phase Kinase-Associated Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27