Impact of E27X, a novel CDKN2A germ line mutation, on p16 and p14ARF expression in Italian melanoma families displaying pancreatic cancer and neuroblastoma

Paola Ghiorzo, Sara Gargiulo, Lorenza Pastorino, Sabina Nasti, Roberto Cusano, William Bruno, Sara Gliori, Mario R. Sertoli, Anna Burroni, Vincenzo Savarino, Francesca Gensini, Roberta Sestini, Paola Queirolo, Alisa M. Goldstein, Giovanna Bianchi Scarrà

Research output: Contribution to journalArticle

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 1α provides interesting insights towards clarifying the mechanisms by which the CDKN2A/ARF locus is involved in cancer predisposition.

Original languageEnglish
Pages (from-to)2682-2689
Number of pages8
JournalHuman Molecular Genetics
Volume15
Issue number18
DOIs
Publication statusPublished - Sep 15 2006

ASJC Scopus subject areas

  • Genetics

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    Ghiorzo, P., Gargiulo, S., Pastorino, L., Nasti, S., Cusano, R., Bruno, W., Gliori, S., Sertoli, M. R., Burroni, A., Savarino, V., Gensini, F., Sestini, R., Queirolo, P., Goldstein, A. M., & Scarrà, G. B. (2006). Impact of E27X, a novel CDKN2A germ line mutation, on p16 and p14ARF expression in Italian melanoma families displaying pancreatic cancer and neuroblastoma. Human Molecular Genetics, 15(18), 2682-2689. https://doi.org/10.1093/hmg/ddl199