title: Absence of germline CDKN2A mutation in Sicilian patients with familial malignant melanoma: Could it be a population-specific genetic signature?
abstract: Germline CDKN2A mutations have been described in 25% to 40% of melanoma families from several countries. Sicilian population is genetically different from the people of Europe and Northern Italy because of its historical background, therefore familial melanoma could be due to genes different from high-penetrance CDKN2A gene. Four hundred patients with cutaneous melanoma were observed in a 6-years period at the Plastic Surgery Unit of the University of Palermo. Forty-eight patients have met the criteria of the Italian Society of Human Genetics (SIGU) for the diagnosis of familial melanoma and were screened for CDKN2A and CDK4 mutations. Mutation testing revealed that none of the families carried mutations in CDK4 and only one patient harboured the rare CDKN2A p.R87W mutation. Unlike other studies, we have not found high mutation rate of CDKN2A in patients affected by familial melanoma or multiple melanoma. This difference could be attributed to different factors, including the genetic heterogeneity of the Sicilian population. It is likely that, as in the Australian people, the inheritance of familial melanoma in this island of the Mediterranean Sea is due to intermediate/low-penetrance susceptibility genes, which, together with environmental factors (as latitude and sun exposure), could determine the occurrence of melanoma.
authors.affiliation: a Department of Surgical , Oncological and Oral Sciences, Section of Plastic Surgery, University of Palermo , 90127 Palermo , Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Di Lorenzo
authors.affiliation: b Department of Surgical , Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo , 90127 Palermo , Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Fanale
authors.affiliation: a Department of Surgical , Oncological and Oral Sciences, Section of Plastic Surgery, University of Palermo , 90127 Palermo , Italy.
authors.forename: Bartolo
authors.initials: B
authors.lastname: Corradino
authors.affiliation: b Department of Surgical , Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo , 90127 Palermo , Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Caló
authors.affiliation: b Department of Surgical , Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo , 90127 Palermo , Italy.
authors.forename: Gaetana
authors.initials: G
authors.lastname: Rinaldi
authors.affiliation: b Department of Surgical , Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo , 90127 Palermo , Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Bazan
authors.affiliation: c Sbarro Institute for Cancer Research and Molecular Medicine, Temple University , Philadelphia , PA 19122 , USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
authors.affiliation: a Department of Surgical , Oncological and Oral Sciences, Section of Plastic Surgery, University of Palermo , 90127 Palermo , Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Cordova
authors.affiliation: b Department of Surgical , Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo , 90127 Palermo , Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
mesh_terms: D000328:Adult; D000368:Aged; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007558:Italy; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D012802:Sicily; D015398:Signal Transduction; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D025803:Tumor Suppressor Protein p14ARF
keywords: CDKN2A; cutaneous melanoma; familial melanoma; germline mutation; p.R87W mutation; p14ARF; p16INK4a