title: Impact of E27X, a novel CDKN2A germ line mutation, on p16 and p14ARF expression in Italian melanoma families displaying pancreatic cancer and neuroblastoma.
abstract: Mutations in the CDKN2A gene underlie melanoma susceptibility in as many as 50% of melanoma kindreds in selected populations, and several CDKN2A founder mutations have been described. Inherited mutations in CDKN2A have been found to be associated with other, non-melanoma cancers including pancreatic cancer (PC) and neural system tumors (NST). Here we report a novel germline mutation in exon 1 of the CDKN2A gene, E27X, which we first detected in melanoma patients living in or originally from a small geographic area bordering Liguria in north-western Italy. A subset of melanoma kindreds positive for this mutation displayed PC and neuroblastoma. E27X generates a premature stop codon, leading to dramatically reduced protein levels of p16 and leaving p14ARF unaltered. As PC and NSTs have been postulated to be preferentially associated with CDKN2A mutations located in exon 2 and/or affecting p14ARF alone, the position of E27X in exon 1alpha provides interesting insights towards clarifying the mechanisms by which the CDKN2A/ARF locus is involved in cancer predisposition.
authors.affiliation: Department of Oncology, Biology and Genetics/Medical Genetics Service, University of Genoa, and Dermatology Unit, San Martino Hospital, Italy. paola.ghiorzo@unige.it
authors.forename: Paola
authors.initials: P
authors.lastname: Ghiorzo
authors.forename: Sara
authors.initials: S
authors.lastname: Gargiulo
authors.forename: Lorenza
authors.initials: L
authors.lastname: Pastorino
authors.forename: Sabina
authors.initials: S
authors.lastname: Nasti
authors.forename: Roberto
authors.initials: R
authors.lastname: Cusano
authors.forename: William
authors.initials: W
authors.lastname: Bruno
authors.forename: Sara
authors.initials: S
authors.lastname: Gliori
authors.forename: Mario R
authors.initials: MR
authors.lastname: Sertoli
authors.forename: Anna
authors.initials: A
authors.lastname: Burroni
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Savarino
authors.forename: Francesca
authors.initials: F
authors.lastname: Gensini
authors.forename: Roberta
authors.initials: R
authors.lastname: Sestini
authors.forename: Paola
authors.initials: P
authors.lastname: Queirolo
authors.forename: Alisa M
authors.initials: AM
authors.lastname: Goldstein
authors.forename: Giovanna Bianchi
authors.initials: GB
authors.lastname: Scarrà
mesh_terms: D000328:Adult; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D005260:Female; D019942:Genes, p16; D005838:Genotype; D018095:Germ-Line Mutation; D006239:Haplotypes; D006801:Humans; D007558:Italy; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D017354:Point Mutation; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics* / Q000378:metabolism
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D025803:Tumor Suppressor Protein p14ARF