Investigation of a putative melanoma susceptibility locus at chromosome 3q29.
Malignant melanoma, the most fatal form of skin cancer, is currently increasing in incidence in many populations. Approximately 10% of all cases occur in families with an inherited predisposition for melanoma. In Sweden, only a minor portion of such melanoma families carry a mutation in the known melanoma gene CDKN2A, and there is a need to identify additional melanoma susceptibility genes. In a recently performed genome-wide linkage screen, novel loci with suggestive evidence of linkage to melanoma were detected. In this study, we have further analyzed one region on chromosome 3q29. In all, 89 affected and 15 nonaffected family members from 42 melanoma-prone families were genotyped for 34 genetic markers. In a pooled linkage analysis of all 42 families, we detected significant evidence of linkage, with a maximum heterogeneity logarithm of odds (HLOD) score of 3.1 with 83% of the families contributing to the linkage score. The minimum critical region of linkage (defined by a 1LOD score support interval) maps to chromosome 3q29, spans 3.5 Mb of genomic sequence, and harbors 44 identified genes. Sequence variants within this region have previously been associated with cancer susceptibility. This study reports the presence of a putative novel melanoma susceptibility locus in the Swedish population, a finding that needs to be replicated in an independent study on other individuals with familial melanoma. Sequencing of genes in the region may identify novel melanoma-associated mutations.
Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
Rainer
R
Tuominen
Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden.
Göran
G
Jönsson
Division of Cell Biology and Dermatology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Charlotta
C
Enerbäck
Department of Clinical Genetics, Sahlgrenska University Hospital, Göteborg, Sweden.
Frida
F
Appelqvist
Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden.
Håkan
H
Olsson
Department of Surgery, Lund University, Lund, Sweden.
Christian
C
Ingvar
Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
Johan
J
Hansson
Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden. Electronic address: veronica.hoiom@ki.se.
Veronica
V
Höiom
D002893:Chromosomes, Human, Pair 3; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008126:Lod Score; D008545:Melanoma / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*
Candidate genes; familial cancer; linkage analysis; melanoma; susceptibility locus