Abstract
Conjunctival melanoma is a rare but potentially deadly tumor of the eye. Despite effective local therapies, recurrence and metastasis remain frequent. Once the tumor has metastasized, treatment options are limited and the prognosis is poor. To date, little is known of the genetic alterations in conjunctival melanomas. We conducted genetic analysis of 78 conjunctival melanomas, to our knowledge the largest cohort reported to date. An oncogene hotspot array was run on 38 samples, screening for a panel of known cancer-relevant mutations. Thirty tumors were analyzed for genome-wide copy number alterations (CNA) using array-based comparative genomic hybridization. Sanger sequencing of selected target mutations was conducted in all samples. BRAF mutations were identified in 23 of 78 (29%) tumors. NRAS mutations, previously not recognized as relevant in conjunctival melanoma, were detected in 14 of 78 (18%) tumors. We found CNAs affecting various chromosomes distributed across the genome in a pattern reminiscent of cutaneous and mucosal melanoma but differing markedly from uveal melanoma. The presence of NRAS or BRAF mutations in a mutually exclusive pattern in roughly half (47%) of conjunctival melanomas and the pattern of CNAs argue for conjunctival melanoma being closely related to cutaneous and mucosal melanoma but entirely distinct from uveal melanoma. Patients with metastatic conjunctival melanoma should be considered for therapeutic modalities available for metastatic cutaneous and mucosal melanoma including clinical trials of novel agents.
Highlights
Melanoma is a disease with a significant death toll affecting people worldwide [1, 2]
The presence of NRAS or BRAF mutations in a mutually exclusive pattern in roughly half (47%) of conjunctival melanomas and the pattern of copy number alterations (CNA) argue for conjunctival melanoma being closely related to cutaneous and mucosal melanoma but entirely distinct from uveal melanoma
Patients with metastatic conjunctival melanoma should be considered for therapeutic modalities available for metastatic cutaneous and mucosal melanoma including clinical trials of novel agents
Summary
Melanoma is a disease with a significant death toll affecting people worldwide [1, 2]. A number of promAuthors' Affiliations: Departments of 1Dermatology and 2Ophthalmology, Institute of Pathology and Neuropathology, University Hospital, University. Duisburg-Essen, Essen, Germany; 4Institute of Human Genetics, Medical. University of Graz, Graz, Austria; 5Department of Melanoma Medical. Systems Biology, University of Texas MD Anderson Cancer. Houston, Texas; 6Department of Pathology and 7Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York; and 8Department of Ophthalmology, University €bingen, Tu €bingen, Germany Hospital Tu. Note: Supplementary data for this article are available at Clinical Cancer.
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