title: First detection of the melanoma-predisposing proline-48-threonine mutation of p16 in Hungarians: was there a common founder either in Italy or in Hungary?
abstract: The P48T germ line mutation of p16 was detected in a Hungarian multiple primary melanoma patient (deceased at the age of 39) with no affected family members. Genetic analysis of the patient and his family revealed that the patient was homozygous for the mutation, whereas his parents (father currently aged 69 and mother 63), who are free from any malignancies and atypical moles, are both heterozygous for the mutation. Our data suggest that the P48T mutation of p16 is a strong melanoma-predisposing factor, but the fact that the heterozygous mutant parents have not yet exhibited melanoma or atypical moles indicates that the penetrance of this allele might depend on modifying factors. The rare P48T germ line mutation of p16 has been reported previously in only four independent studies, all in patients with Italian ancestry. Here, we first report the inheritance of the rare P48T mutation of CDKN2A in a Hungarian family with a homozygous multiple primary melanoma member and unaffected heterozygous family members. The question of whether the mutation detected in Hungary is the result of an independent event, or migration of the founder mutation occurred at some time in the past, necessitates further investigations.
authors.affiliation: Dermatological Research Group of the Hungarian Academy of Sciences, University of Szeged, Szeged, Hungary. szell@mail.derma.szote.u-szeged.hu
authors.forename: Márta
authors.initials: M
authors.lastname: Széll
authors.forename: Klára
authors.initials: K
authors.lastname: Balogh
authors.forename: Attila
authors.initials: A
authors.lastname: Dobozy
authors.forename: Lajos
authors.initials: L
authors.lastname: Kemény
authors.forename: Judit
authors.initials: J
authors.lastname: Oláh
mesh_terms: D000328:Adult; D001483:Base Sequence; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000737:chemistry / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D018095:Germ-Line Mutation; D006801:Humans; D006814:Hungary; D007558:Italy; D008297:Male; D008545:Melanoma / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics*; D008969:Molecular Sequence Data; D011392:Proline / Q000737:chemistry*; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics*; D013912:Threonine / Q000737:chemistry*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D013912:Threonine; D011392:Proline