title: Are all melanomas the same? Spitzoid melanoma is a distinct subtype of melanoma.
abstract: BACKGROUND
  Although the majority of melanomas demonstrate high rates of mutations in B-RAF or N-RAS that result in constitutive activation of the mitogen-activated protein kinase-signaling pathway, emerging data suggest molecular differences among melanoma subtypes. In this study, the authors evaluated the contribution of B-RAF and N-RAS mutations to the pathogenesis of Spitzoid melanomas.
  
  
  METHODS
  In total, 33 Spitzoid melanomas were analyzed for clinical and pathologic characteristics as well as for hot-spot mutations in the B-RAF and N-RAS genes. In the majority of patients (28 of 33 melanomas), the tumors were confined to the skin with no evidence of metastasis (average follow-up, 32.5 mos). There were five metastasizing melanomas (5 of 33 tumors) with regional or systemic spread.
  
  
  RESULTS
  Of 33 Spitzoid melanomas, only 1 showed the V600E mutation in the B-RAF gene (1 of 33 tumors; 3%). It was noteworthy that none of the metastatic Spitzoid melanomas (0 of 5 tumors; 0%), of which 2 resulted in fatal outcomes, demonstrated mutations in B-RAF or N-RAS.
  
  
  CONCLUSIONS
  In contrast to the majority of cutaneous melanomas, activating hot-spot mutations in B-RAF or N-RAS were not involved in the pathogenesis of Spitzoid melanoma. These data suggested that Spitzoid melanoma is a distinct form of melanoma with unknown genes and/or signaling pathways involved in its development.
authors.affiliation: Department of Dermatology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Lee
authors.forename: Jason A
authors.initials: JA
authors.lastname: Cohen
authors.forename: William S
authors.initials: WS
authors.lastname: Twaddell
authors.forename: Gustavo
authors.initials: G
authors.lastname: Palacios
authors.forename: Melissa
authors.initials: M
authors.lastname: Gill
authors.forename: Eyal
authors.initials: E
authors.lastname: Levit
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Halperin
authors.forename: Joan
authors.initials: J
authors.lastname: Mones
authors.forename: Klaus J
authors.initials: KJ
authors.lastname: Busam
authors.forename: David N
authors.initials: DN
authors.lastname: Silvers
authors.forename: Julide Tok
authors.initials: JT
authors.lastname: Celebi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D011905:Genes, ras; D006801:Humans; D008297:Male; D008545:Melanoma / Q000145:classification / Q000235:genetics* / Q000503:physiopathology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000145:classification / Q000235:genetics* / Q000503:physiopathology*
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020928:Mitogen-Activated Protein Kinases