title: Heterogeneous distribution of BRAF/NRAS mutations among Italian patients with advanced melanoma.
abstract: BACKGROUND
  Prevalence and distribution of pathogenetic mutations in BRAF and NRAS genes were evaluated in multiple melanoma lesions from patients with different geographical origin within the same Italian population.
  
  
  METHODS
  Genomic DNA from a total of 749 tumor samples (451 primary tumors and 298 metastases) in 513 consecutively-collected patients with advanced melanoma (AJCC stages III and IV) was screened for mutations in exon 15 of BRAF gene and, at lower extension (354/513; 69%), in the entire coding DNA of NRAS gene by automated direct sequencing. Among tissues, 236 paired samples of primary melanomas and synchronous or asynchronous metastases were included into the screening.
  
  
  RESULTS
  Overall, mutations were detected in 49% primary melanomas and 51% metastases, for BRAF gene, and 15% primary tumors and 16% secondaries, for NRAS gene. A heterogeneous distribution of mutations in both genes was observed among the 451 primary melanomas according to patients' geographical origin: 61% vs. 42% (p = 0.0372) BRAF-mutated patients and 2% vs. 21% (p < 0.0001) NRAS-mutated cases were observed in Sardinian and non-Sardinian populations, respectively. Consistency in BRAF/NRAS mutations among paired samples was high for lymph node (91%) and visceral metastases (92.5%), but significantly lower for brain (79%; p = 0.0227) and skin (71%; p = 0.0009) metastases.
  
  
  CONCLUSIONS
  Our findings about the two main alterations occurring in the different tumor tissues from patients with advanced melanoma may be helpful in improving the management of such a disease.
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: Maria
authors.initials: M
authors.lastname: Colombino
authors.forename: Amelia
authors.initials: A
authors.lastname: Lissia
authors.forename: Mariaelena
authors.initials: M
authors.lastname: Capone
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Giorgi
authors.forename: Daniela
authors.initials: D
authors.lastname: Massi
authors.forename: Ignazio
authors.initials: I
authors.lastname: Stanganelli
authors.forename: Ester
authors.initials: E
authors.lastname: Fonsatti
authors.forename: Michele
authors.initials: M
authors.lastname: Maio
authors.forename: Gerardo
authors.initials: G
authors.lastname: Botti
authors.forename: Corrado
authors.initials: C
authors.lastname: Caracò
authors.forename: Nicola
authors.initials: N
authors.lastname: Mozzillo
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Ascierto
authors.forename: Antonio
authors.initials: A
authors.lastname: Cossu
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palmieri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D007558:Italy; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D015995:Prevalence; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human