title: Mapping of a novel ocular and cutaneous malignant melanoma susceptibility locus to chromosome 9q21.32.
abstract: An estimated 10% of all cutaneous malignant melanoma (CMM) cases are inherited, but the genetics of familial CMM are largely unknown. Ocular malignant melanoma (OMM), which is rare, may be associated with familial CMM. We performed a genome-wide scan of two Danish pedigrees with multiple cases of OMM (N = 10) and CMM (N = 3) and other malignancies (with no germline mutations in CDKN2A, CDK4, BRCA1, and BRCA2) to identify melanoma susceptibility genes. Results of parametric linkage analysis are presented as logarithm of the odds (LOD) scores, and all P values are two-sided. Peak two-point parametric LOD score of 2.2 (P = .0007) at D9S167 on chromosome 9q21 was observed. Targeted analysis of a third Danish family with OMM and CMM patients confirmed 9q21 linkage, providing a combined four-point parametric LOD score of 3.02 (nominal P = .00003 and genome-wide P = .086). Two families shared a common haplotype comprising three adjacent and highly polymorphic markers, limiting the region to less than 5 cM and 3 Mbp at 9q21.32. Expression of RASEF, a known gene in this region, was examined in tumor tissue from 10 sporadic CMM lesions and was found to be decreased in 70% of these tumors compared with RASEF expression in a human reference RNA pool from 10 different cell types and in 10 breast tumors.
authors.affiliation: Department of Oncology, University Hospital, Lund, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Jönsson
authors.forename: Pär-Ola
authors.initials: PO
authors.lastname: Bendahl
authors.forename: Therese
authors.initials: T
authors.lastname: Sandberg
authors.forename: Azra
authors.initials: A
authors.lastname: Kurbasic
authors.forename: Johan
authors.initials: J
authors.lastname: Staaf
authors.forename: Lone
authors.initials: L
authors.lastname: Sunde
authors.forename: Dorthe G
authors.initials: DG
authors.lastname: Crüger
authors.forename: Christian
authors.initials: C
authors.lastname: Ingvar
authors.forename: Håkan
authors.initials: H
authors.lastname: Olsson
authors.forename: Ake
authors.initials: A
authors.lastname: Borg
mesh_terms: D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D003718:Denmark; D005134:Eye Neoplasms / Q000235:genetics*; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008126:Lod Score; D008545:Melanoma / Q000235:genetics*; D010375:Pedigree; D012878:Skin Neoplasms / Q000235:genetics*