title: Increased C-MYC copy numbers on the background of CDKN2A loss is associated with improved survival in nodular melanoma.
abstract: OBJECTIVE
  In order to obtain better insight into the genetic background of nodular melanoma (NM), we aimed to analyse the frequency of CDKN2A and C-MYC copy number changes. The impact of these aberrations on the metastatic potential and patient's survival was considered.
  
  
  METHODS
  Fluorescent in situ hybridization was used to analyse the C-MYC and CDKN2A genes on isolated nuclei from 49 paraffin-embedded primary NMs.
  
  
  RESULTS
  Thirty-six (73.47%) melanoma samples showed CDKN2A deletion while 11 of these 36 (22.45%) additionally displayed C-MYC increased copy numbers. Cases positive for metastases more commonly displayed CDKN2A deletions. However, the combined C-MYC and CDKN2A aberrations were found predominantly in the non-metastasizing group of primary NM. The survival analysis furthermore demonstrated that patients with combined CDKN2A and C-MYC aberrations have a significantly better prognosis than carriers of CDKN2A deletion only.
  
  
  CONCLUSIONS
  We conclude that the C-MYC increased copy number changes on the background of CDKN2A deletions seem to be related to a low metastatic potential and better patients' outcome in primary NMs.
authors.affiliation: Department of Medical Genetics, Medical University Sofia, 2 Zdrave Str, 1431, Sofia, Bulgaria. dkkoinova@abv.bg
authors.forename: Denitsa
authors.initials: D
authors.lastname: Koynova
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Jordanova
authors.forename: Nicole
authors.initials: N
authors.lastname: Kukutsch
authors.forename: Pieter
authors.initials: P
authors.lastname: van der Velden
authors.forename: Draga
authors.initials: D
authors.lastname: Toncheva
authors.forename: Nelleke
authors.initials: N
authors.lastname: Gruis
mesh_terms: D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D016259:Genes, myc; D019942:Genes, p16; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000401:mortality* / Q000473:pathology