title: CDKN2A mutations in Scottish families with cutaneous melanoma: results from 32 newly identified families.
abstract: BACKGROUND
  Up to 5% of patients with melanoma have a family history of a first-degree relative also being affected.
  
  
  OBJECTIVE
  To study such families for germline mutations, to help clarify the gene-environment interaction in melanoma aetiology.
  
  
  METHODS
  Thirty-two families in Scotland with melanoma in two or more first-degree relatives are reported for the first time. Peripheral blood DNA was extracted, and denaturing high-performance liquid chromatography analysis performed on exons 1alpha and 2 of the CDKN2A gene and their splice junctions. The coding sequences and splice junctions of these exons were sequenced in all samples as confirmation of the chromatographic pattern observed.
  
  
  RESULTS
  Seven of the 32 melanoma families (22%) have CDKN2A mutations. One mutation, H83N, which has not previously been described in melanoma families, was found in one family. In addition, two families have R112G mutations, one family has a G67R mutation, one has an exon 1alpha 24-bp duplication where bases 9-32 are duplicated between bases 32 and 33, and two families have M53I mutations, bringing the total of known Scottish families with the M53I mutation to six.
  
  
  CONCLUSIONS
  This study brings the total of Scottish families investigated for germline mutations to 48, and strongly suggests that the M53I mutation originated in Scotland.
authors.affiliation: Duncan Guthrie Institute of Medical Genetics, Royal Hospital for Sick Children and University of Glasgow, Glasgow, Scotland, U.K.
authors.forename: J
authors.initials: J
authors.lastname: Lang
authors.forename: M
authors.initials: M
authors.lastname: Boxer
authors.forename: R M
authors.initials: RM
authors.lastname: MacKie
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis / Q000379:methods; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D019942:Genes, p16; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D010375:Pedigree; D012878:Skin Neoplasms / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm