title: A germline deletion of p14(ARF) but not CDKN2A in a melanoma-neural system tumour syndrome family.
abstract: The melanoma-astrocytoma syndrome is characterized by a dual predisposition to melanoma and neural system tumours, commonly astrocytoma. Germline deletions of the region on 9p21 containing the CDKN2A and CDKN2B genes and CDKN2A exon 1beta have been reported in kindreds, implicating contiguous tumour suppressor gene deletion as a cause of this syndrome. We describe a family characterized by multiple melanoma and neural cell tumours segregating with a germline deletion of the p14(ARF)-specific exon 1beta of the CDKN2A gene. This deletion does not affect the coding or minimal promoter sequences of either the CDKN2A or CDKN2B genes. Our results are consistent with either: (i) loss of p14(ARF) function being the critical abnormality associated with this syndrome, rather than contiguous loss of both the CDKN2A and CDKN2B genes as suggested previously; or (ii) disruption of expression of p16 by mechanisms as yet unknown.
authors.affiliation: ICRF Genetic Epidemiology Division, ICRF Clinical Centre in Leeds, Cancer Genetics Building, St James's University Hospital, Beckett Street, Leeds LS9 7TF, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: Randerson-Moor
authors.forename: M
authors.initials: M
authors.lastname: Harland
authors.forename: S
authors.initials: S
authors.lastname: Williams
authors.forename: D
authors.initials: D
authors.lastname: Cuthbert-Heavens
authors.forename: E
authors.initials: E
authors.lastname: Sheridan
authors.forename: J
authors.initials: J
authors.lastname: Aveyard
authors.forename: K
authors.initials: K
authors.lastname: Sibley
authors.forename: L
authors.initials: L
authors.lastname: Whitaker
authors.forename: M
authors.initials: M
authors.lastname: Knowles
authors.forename: J N
authors.initials: JN
authors.lastname: Bishop
authors.forename: D T
authors.initials: DT
authors.lastname: Bishop
mesh_terms: D001254:Astrocytoma / Q000235:genetics*; D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics*; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D003360:Cosmids; D005091:Exons; D005192:Family Health; D005260:Female; D017353:Gene Deletion; D019942:Genes, p16 / Q000235:genetics*; D018095:Germ-Line Mutation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008545:Melanoma / Q000235:genetics*; D018895:Microsatellite Repeats; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D015183:Restriction Mapping; D025803:Tumor Suppressor Protein p14ARF
chemical_list: D011506:Proteins; D025803:Tumor Suppressor Protein p14ARF