title: Conjunctival melanomas harbor BRAF and NRAS mutations and copy number changes similar to cutaneous and mucosal melanomas.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Dermatology, Institute of Pathology and Neuropathology, University Hospital, University Duisburg-Essen, Essen, Germany.
authors: Klaus G
authors: KG
authors: Griewank
authors: Henrike
authors: H
authors: Westekemper
authors: Rajmohan
authors: R
authors: Murali
authors: Monika
authors: M
authors: Mach
authors: Bastian
authors: B
authors: Schilling
authors: Thomas
authors: T
authors: Wiesner
authors: Tobias
authors: T
authors: Schimming
authors: Elisabeth
authors: E
authors: Livingstone
authors: Antje
authors: A
authors: Sucker
authors: Florian
authors: F
authors: Grabellus
authors: Claudia
authors: C
authors: Metz
authors: Daniela
authors: D
authors: Süsskind
authors: Uwe
authors: U
authors: Hillen
authors: Michael R
authors: MR
authors: Speicher
authors: Scott E
authors: SE
authors: Woodman
authors: Klaus-Peter
authors: KP
authors: Steuhl
authors: Dirk
authors: D
authors: Schadendorf
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D055028:Comparative Genomic Hybridization; D003230:Conjunctival Neoplasms / Q000235:genetics* / Q000473:pathology; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012867:Skin / Q000473:pathology
chemical_list: D008565:Membrane Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human