title: Haplotype analysis of two recurrent CDKN2A mutations in 10 melanoma families: evidence for common founders and independent mutations.
abstract: Germ-line mutations in CDKN2A have been shown to predispose to cutaneous malignant melanoma. We have identified 2 new melanoma kindreds which carry a duplication of a 24bp repeat present in the 5' region of CDKN2A previously identified in melanoma families from Australia and the United States. This mutation has now been reported in 5 melanoma families from 3 continents: Europe, North America, and Australasia. The M53I mutation in exon 2 of CDKN2A has also been documented in 5 melanoma families from Australia and North America. The aim of this study was to determine whether the occurrence of the mutations in these families from geographically diverse populations represented mutation hotspots within CDKN2A or were due to common ancestors. Haplotypes of 11 microsatellite markers flanking CDKN2A were constructed in 5 families carrying the M53I mutation and 5 families carrying the 24bp duplication. There were some differences in the segregating haplotypes due primarily to recombinations and mutations within the short tandem-repeat markers; however, the data provide evidence to indicate that there were at least 3 independent 24bp duplication events and possibly only 1 original M53I mutation. This is the first study to date which indicates common founders in melanoma families from different continents.
authors.affiliation: Queensland Cancer Fund Research Unit, Joint Experimental Oncology Program, Queensland Institute of Medical Research, Brisbane, Australia.
authors.forename: P M
authors.initials: PM
authors.lastname: Pollock
authors.forename: N
authors.initials: N
authors.lastname: Spurr
authors.forename: T
authors.initials: T
authors.lastname: Bishop
authors.forename: J
authors.initials: J
authors.lastname: Newton-Bishop
authors.forename: N
authors.initials: N
authors.lastname: Gruis
authors.forename: P A
authors.initials: PA
authors.lastname: van der Velden
authors.forename: A M
authors.initials: AM
authors.lastname: Goldstein
authors.forename: M A
authors.initials: MA
authors.lastname: Tucker
authors.forename: W D
authors.initials: WD
authors.lastname: Foulkes
authors.forename: R
authors.initials: R
authors.lastname: Barnhill
authors.forename: D
authors.initials: D
authors.lastname: Haber
authors.forename: J
authors.initials: J
authors.lastname: Fountain
authors.forename: N K
authors.initials: NK
authors.lastname: Hayward
mesh_terms: D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D018703:Founder Effect; D005819:Genetic Markers; D005838:Genotype; D018095:Germ-Line Mutation; D005858:Germany; D006239:Haplotypes; D008545:Melanoma / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D005810:Multigene Family; D012878:Skin Neoplasms / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D006113:United Kingdom
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D005819:Genetic Markers