title: Further evidence for a locus for cutaneous malignant melanoma-dysplastic nevus (CMM/DN) on chromosome 1p, and evidence for genetic heterogeneity.
abstract: Assignment of a susceptibility locus for cutaneous malignant melanoma-dysplastic nevus (CMM/DN) to chromosome 1p remains controversial. We examined the relationship between CMM/DN and markers D1S47, PND, and D1S160 on seven new families (set B) plus updated versions of six previously reported families (set A). Three linkage analyses were performed: (1) CMM alone--all individuals without confirmed melanoma or borderline lesions were considered unaffected (model I); (2) CMM/DN with variable age at onset and sporadics (model II); and (3) CMM/DN using the model of Bale et al. (model III). For CMM alone and D1S47, Zmax = 3.12 at theta = .10. For D1S160 and CMM alone, Zmax = 1.76 at theta = .10. PND showed no evidence for linkage to CMM alone. Models II and III showed strong evidence for linkage to D1S47, D1S160, and PND in the set A pedigrees but not in the set B families. We tested for homogeneity of CMM/DN (model II) by splitting families into two groups on the basis of (1) the proportion of CMM/DN cases and (2) the occurrence of immune-related tumors. In group 1 there was significant evidence of heterogeneity with both D1S47 and D1S160, and in group 2 there was significant evidence of heterogeneity with D1S160. Thus, diagnostic, clinical, and genetic heterogeneity are the likely reasons that previous studies have failed to confirm linkage of CMM/DN to chromosome 1p. The results showed significant evidence for a CMM locus linked to D1S47, as well as significant evidence for heterogeneity with only a subset of the families appearing linked to chromosome 1p.
authors.affiliation: Family Studies Section, National Cancer Institute, Bethesda, MD 20892.
authors.forename: A M
authors.initials: AM
authors.lastname: Goldstein
authors.forename: N C
authors.initials: NC
authors.lastname: Dracopoli
authors.forename: E C
authors.initials: EC
authors.lastname: Ho
authors.forename: M C
authors.initials: MC
authors.lastname: Fraser
authors.forename: K S
authors.initials: KS
authors.lastname: Kearns
authors.forename: S J
authors.initials: SJ
authors.lastname: Bale
authors.forename: O W
authors.initials: OW
authors.lastname: McBride
authors.forename: W H
authors.initials: WH
authors.lastname: Clark
authors.forename: M A
authors.initials: MA
authors.lastname: Tucker
mesh_terms: D000328:Adult; D015139:Blotting, Southern; D002878:Chromosomes, Human, Pair 1; D004247:DNA / Q000235:genetics; D015342:DNA Probes; D004416:Dysplastic Nevus Syndrome / Q000235:genetics*; D005190:Family; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D010375:Pedigree
chemical_list: D015342:DNA Probes; D005819:Genetic Markers; D004247:DNA