Role of Elevated PHIP Copy Number as a Prognostic and Progression Marker for Cutaneous Melanoma

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Vladimir BezrookoveMohammed Kashani-Sabet

Abstract

Purpose: Previous studies have indicated an important role for pleckstrin homology domain-interacting protein (PHIP) as a marker and mediator of melanoma metastasis. Here we aimed to confirm the role of PHIP copy number in successive stages of melanoma progression.Experimental Design:PHIP copy number was examined using FISH in three independent cohorts by recording the percentage of cells harboring ≥3 copies of PHIP The impact of PHIP copy number on survival was assessed using Cox regression analysis. The enrichment of PHIP was assessed in various molecular melanoma subtypes. PHIP expression was analyzed in The Cancer Genome Atlas (TCGA) melanoma cohort.Results: Elevated PHIP copy number was significantly predictive of reduced distant metastasis-free survival (DMFS) and disease-specific survival (DSS), and increased prevalence of ulceration in primary melanoma (cohort No. 1). By multivariate analysis, PHIP FISH scores were independently predictive of DMFS and DSS. PHIP copy number was enriched in metastatic melanomas harboring mutant NRAS or expressing PTEN protein (cohort No. 2). PHIP copy number was significantly elevated in metastatic melanomas when compared with matched primary tumors from the same patient (cohort No. 3). S...Continue Reading

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Citations

Dec 14, 2018·Oncotarget·Mohammed Kashani-SabetDavid de Semir
Apr 11, 2020·Proceedings of the National Academy of Sciences of the United States of America·David de SemirMohammed Kashani-Sabet
Jan 5, 2022·Photodermatology, Photoimmunology & Photomedicine·Liang DingGyorgy Paragh

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