title: Alterations in CDKN2A locus as potential indicator of melanoma predisposition in relatives of non-familial melanoma cases.
abstract: OBJECTIVE
  To examine constitutional alterations of CDKN2A/p16INK4A locus as a potential indicator of melanoma predisposition among the first-degree relatives of patients with malignant melanoma.
  
  
  METHODS
  The study included eight families with a single member affected with melanoma. Members of the families were screened for allelic cosegregation with 9p21 region polymorphic markers IFNA, D9S126, and D9S104. The patient's tumors were screened for loss of heterozygosity (LOH) with the same markers, as well as for single strand conformational polymorphism (SSCP) variability of CDKN2A. In suspect cases, constitutional DNA was examined by SSCP and direct sequencing.
  
  
  RESULTS
  LOH was detected in four cases, and SSCP indicated variability in at least one CDKN2A exon in these tumor samples. In three of four LOH cases, the remaining allele cosegregated within the family, which was interpreted as a preliminary indicator of potential genetic predisposition. In one of these three families, we found constitutional CDKN2A mutations in the patient and one of the relatives. In the second family, only the patient had the constitutionally altered gene, whereas no constitutional CDKN2A alterations were detected in the third family. All significant mutations were different and had not been reported before.
  
  
  CONCLUSIONS
  We detected one case of melanoma predisposition among unaffected family members, which corresponded to statistical expectations for such a small number of screened families. Since constitutional mutations of CDKN2A exons have limited incidence, our stepwise approach seemed to be more informative and more affordable than straightforward CDKN2A sequencing of all subjects.
authors.affiliation: Division of Molecular Medicine, Ruder Bosković Institute, Bijenicka 54, 10000 Zagreb, Croatia. levanat@rudjer.irb.hr
authors.forename: Sonja
authors.initials: S
authors.lastname: Levanat
authors.forename: Mirna
authors.initials: M
authors.lastname: Situm
authors.forename: Ivana
authors.initials: I
authors.lastname: Crnić
authors.forename: Dujomir
authors.initials: D
authors.lastname: Marasović
authors.forename: Neira
authors.initials: N
authors.lastname: Puizina-Ivić
authors.forename: Nikola
authors.initials: N
authors.lastname: Pokupcić
authors.forename: Vesna
authors.initials: V
authors.lastname: Musani
authors.forename: Arijana
authors.initials: A
authors.lastname: Komar
authors.forename: Milovan
authors.initials: M
authors.lastname: Kubat
authors.forename: Ivana
authors.initials: I
authors.lastname: Furac
authors.forename: Monika
authors.initials: M
authors.lastname: Karija-Vlahović
authors.forename: Simun
authors.initials: S
authors.lastname: Krizanac
mesh_terms: D000483:Alleles; D001483:Base Sequence; D001707:Biopsy, Needle; D017523:Croatia; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D019942:Genes, p16; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D010375:Pedigree; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm