title: Molecular alterations at chromosome 9p21 in melanocytic naevi and melanoma.
abstract: BACKGROUND
  The chromosome 9p21 and its CDKN locus, with the p16 tumour suppressor gene (CDKN2A), are recognized as the genomic regions involved in the pathogenesis of melanoma.
  
  
  OBJECTIVE
  To elucidate further the role of such regions during the different phases of melanocytic tumorigenesis.
  
  
  METHODS
  Tissue sections from naevi, primary and metastatic melanomas were investigated by fluorescence in situ hybridization for allelic loss at the 9p21 chromosome and by immunochemistry for p16CDKN2A expression.
  
  
  RESULTS
  Dysplastic naevi and primary or secondary melanomas were found to carry hemizygous deletions within the entire 9p21 region at similar frequencies (varying from 55% to 62%). Allelic deletion spanning the CDKN locus was observed at significantly increased rates moving from early (7%) to advanced (28%) primary melanomas and to secondary melanoma lesions (37%) (P=0.018). Also, inactivation of the p16 gene (CDKN2A) was absent in naevi and present at steadily increasing rates moving from primary melanomas (7% early lesions to 17% advanced lesions) to melanoma metastases (62%) (P=0.004).
  
  
  CONCLUSIONS
  Our findings indicate that, in a model of sequential accumulation of genetic alterations, 9p21 deletions may play a role in melanocytic transformation and tumour initiation whereas rearrangements at the CDKN locus, and p16 gene (CDKN2A) inactivation may contribute to tumour progression.
authors.affiliation: Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Traversa La Crucca 3-Regione Baldinca, 07040 Li Punti-Sassari, Italy.
authors.forename: M C
authors.initials: MC
authors.lastname: Sini
authors.forename: A
authors.initials: A
authors.lastname: Manca
authors.forename: A
authors.initials: A
authors.lastname: Cossu
authors.forename: M
authors.initials: M
authors.lastname: Budroni
authors.forename: G
authors.initials: G
authors.lastname: Botti
authors.forename: P A
authors.initials: PA
authors.lastname: Ascierto
authors.forename: F
authors.initials: F
authors.lastname: Cremona
authors.forename: A
authors.initials: A
authors.lastname: Muggiano
authors.forename: S
authors.initials: S
authors.lastname: D'Atri
authors.forename: M
authors.initials: M
authors.lastname: Casula
authors.forename: P
authors.initials: P
authors.lastname: Baldinu
authors.forename: G
authors.initials: G
authors.lastname: Palomba
authors.forename: A
authors.initials: A
authors.lastname: Lissia
authors.forename: F
authors.initials: F
authors.lastname: Tanda
authors.forename: G
authors.initials: G
authors.lastname: Palmieri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D005260:Female; D019942:Genes, p16; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007558:Italy; D019656:Loss of Heterozygosity; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D009508:Nevus, Pigmented / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*