Human Molecular Genetics Advance Access published online on August 7, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl199
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1 Department of Oncology, Biology and Genetics/Medical Genetics Service, University of Genoa, V.le Benedetto XV, 6, 16129 Italy
* To whom correspondence should be addressed. 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 and neural system tumors. 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 pancreatic cancer and neuroblastoma. E27X generates a premature stop codon, leading to dramatically reduced protein levels of p16 and leaving p14ARF unaltered. As pancreatic cancer and neural system tumors 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 1
Received June 1, 2006
Revised July 27, 2006
Accepted July 27, 2006
Article
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 1 *, Sara Gargiulo 2, Lorenza Pastorino 2, Sabina Nasti 2, Roberto Cusano 2, William Bruno 2, Sara Gliori 3, Mario R. Sertoli 4, Anna Burroni 5, Vincenzo Savarino 6, Francesca Gensini 7, Roberta Sestini 7, Paola Queirolo 3, Alisa M. Goldstein 8, and Giovanna Bianchi Scarrà 2
2 Department of Oncology, Biology and Genetics/Medical Genetics Service, University of Genoa, Italy
3 National Cancer Institute, Genoa, Italy
4 Department of Oncology, Biology and Genetics/Medical Genetics Service, University of Genoa, Italy; National Cancer Institute, Genoa, Italy
5 Dermatology Unit, San Martino Hospital, Genoa, Italy
6 Department of Internal Medicine, University of Genoa, Italy
7 Department of Clinical Pathophysiology/ Medical Genetics Service, University of Florence, Florence, Italy
8 Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, USA
Paola Ghiorzo, E-mail: paola.ghiorzo{at}unige.it
Abstract 
provides interesting insights towards clarifying the mechanisms by which the CDKN2A/ARF locus is involved in cancer predisposition.
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