Michele Massimino1,2, Stefania Stella3,2, Giovanni Micale3, Lucia Motta2,4, Giuliana Pavone2,4, Giuseppe Broggi5, Eliana Piombino6, Gaetano Magro5, Hector Jose Soto Parra4, Livia Manzella3,2, Paolo Vigneri3,2,4. 1. Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy; michedot@yahoo.it. 2. Center of Experimental Oncology and Hematology, A.O.U. Policlinico "G. Rodolico - S. Marco", Catania, Italy. 3. Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy. 4. Medical Oncology, A.O.U. "G. Rodolico - S. Marco", Catania, Italy. 5. Department of Medical, Surgical Sciences and Advanced Technologies "G.F. Ingrassia", Anatomic Pathology, University of Catania, Catania, Italy. 6. Pathology Unit, Department of Experimental Oncology, Mediterranean Institute of Oncology, Viagrande, Italy.
Abstract
BACKGROUND/AIM: Malignant melanoma is a skin cancer originating from the oncogenic transformation of melanocytes located in the epidermal layers. Usually, the patient's prognosis depends on timing of disease detection and molecular and genetic profiling, which may all significantly influence mortality rates. Genetic analyses often detect somatic BRAF, NRAS and cKIT mutations, germline substitutions in CDKN2A, and alterations of the PI3K-AKT-PTEN pathway. A peculiar molecular future of melanoma is its high immunogenicity, making this tumor targetable by programmed cell death protein 1-specific antibodies. MATERIALS AND METHODS: Ten formalin-fixed paraffin embedded samples derived from melanoma patients were subjected to next-generation sequencing (NGS) analysis using the FDA-approved FoundationOne CDx™ test. The molecular features of each case were then analyzed employing several in silico prediction tools. RESULTS: We analyzed the mutational landscape of patients with metastatic or relapsed cutaneous melanoma to define enriched pathways and protein-protein interactions. The analysis showed that both known genetic alterations and variants of unknown significance rely on redundant signaling converging on similar gene ontology biological processes. Complex informatics analyses of NGS-based genetic results identified pivotal signaling pathways that could provide additional targets for cancer treatment. CONCLUSION: Our data suggest an additional role for NGS in melanoma, as analysis of comprehensive genetic findings using innovative informatic tools may lengthen the list of druggable molecular targets that impact patient outcome. Copyright
BACKGROUND/AIM: Malignant melanoma is a skin cancer originating from the oncogenic transformation of melanocytes located in the epidermal layers. Usually, the patient's prognosis depends on timing of disease detection and molecular and genetic profiling, which may all significantly influence mortality rates. Genetic analyses often detect somatic BRAF, NRAS and cKIT mutations, germline substitutions in CDKN2A, and alterations of the PI3K-AKT-PTEN pathway. A peculiar molecular future of melanoma is its high immunogenicity, making this tumor targetable by programmed cell death protein 1-specific antibodies. MATERIALS AND METHODS: Ten formalin-fixed paraffin embedded samples derived from melanoma patients were subjected to next-generation sequencing (NGS) analysis using the FDA-approved FoundationOne CDx™ test. The molecular features of each case were then analyzed employing several in silico prediction tools. RESULTS: We analyzed the mutational landscape of patients with metastatic or relapsed cutaneous melanoma to define enriched pathways and protein-protein interactions. The analysis showed that both known genetic alterations and variants of unknown significance rely on redundant signaling converging on similar gene ontology biological processes. Complex informatics analyses of NGS-based genetic results identified pivotal signaling pathways that could provide additional targets for cancer treatment. CONCLUSION: Our data suggest an additional role for NGS in melanoma, as analysis of comprehensive genetic findings using innovative informatic tools may lengthen the list of druggable molecular targets that impact patient outcome. Copyright
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