title: Discrepant alterations in main candidate genes among multiple primary melanomas.
abstract: BACKGROUND
  Alterations in key-regulator genes of disease pathogenesis (BRAF, cKIT, CyclinD1) have been evaluated in patients with multiple primary melanoma (MPM).
  
  
  METHODS
  One hundred twelve MPM patients (96 cases with two primary melanomas, 15 with three, and 1 with four) were included into the study. Paired synchronous/asynchronous MPM tissues (N=229) were analyzed for BRAF mutations and cKIT/CyclynD1 gene amplifications.
  
  
  RESULTS
  BRAF mutations were identified in 109/229 (48%) primary melanomas, whereas cKIT and CyclinD1 amplifications were observed in 10/216 (5%) and 29/214 (14%) tumor tissues, respectively. While frequency rates of BRAF mutations were quite identical across the different MPM lesions, a significant increase of cKIT (p<0.001) and CyclinD1 (p=0.002) amplification rates was observed between first and subsequent primary melanomas. Among the 107 patients with paired melanoma samples, 53 (49.5%) presented consistent alteration patterns between first and subsequent primary tumors. About one third (40/122; 32.8%) of subsequent melanomas presented a discrepant pattern of BRAF mutations as compared to incident primary tumors.
  
  
  CONCLUSIONS
  The low consistency in somatic mutation patterns among MPM lesions from same patients provides further evidence that melanomagenesis is heterogeneous and different cell types may be involved. This may have implications in clinical practice due to the difficulties in molecularly classifying patients with discrepant primary melanomas.
authors.forename: Maria
authors.initials: M
authors.lastname: Colombino
authors.forename: MariaCristina
authors.initials: M
authors.lastname: Sini
authors.forename: Amelia
authors.initials: A
authors.lastname: Lissia
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Giorgi
authors.forename: Ignazio
authors.initials: I
authors.lastname: Stanganelli
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Ayala
authors.forename: Daniela
authors.initials: D
authors.lastname: Massi
authors.forename: Corrado
authors.initials: C
authors.lastname: Rubino
authors.forename: Antonella
authors.initials: A
authors.lastname: Manca
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Paliogiannis
authors.forename: Susanna
authors.initials: S
authors.lastname: Rossari
authors.forename: Serena
authors.initials: S
authors.lastname: Magi
authors.forename: Laura
authors.initials: L
authors.lastname: Mazzoni
authors.forename: Gerardo
authors.initials: G
authors.lastname: Botti
authors.forename: Mariaelena
authors.initials: M
authors.lastname: Capone
authors.forename: Marco
authors.initials: M
authors.lastname: Palla
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Ascierto
authors.forename: Antonio
authors.initials: A
authors.lastname: Cossu
authors.affiliation: Unit of Cancer Genetics, Institute of Biomolecular Chemistry (ICB), National Research Council (CNR) - Traversa La Crucca 3, Baldinca Li Punti, 07100 Sassari, Italy. gpalmieri@yahoo.com.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palmieri
mesh_terms: D000328:Adult; D019938:Cyclin D1 / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*
chemical_list: D019938:Cyclin D1; D019009:Proto-Oncogene Proteins c-kit; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf