Hereditary melanoma in Australia. Variable association with dysplastic nevi and absence of genetic linkage to chromosome 1p.
Hereditary cutaneous malignant melanoma in association with the presence of multiple precursor lesions termed the dysplastic nevus syndrome (DNS) has been reported to display autosomal dominant inheritance with high penetrance. The gene for this disease was recently assigned to the distal short arm of chromosome 1 on chromosomal band 1p36, 7.6 centimorgans distal to the locus for the pronatrodilatin (PND) gene. We assessed 119 family members of eight newly described Australian families, 30 of whom had cutaneous malignant melanoma. Only eight of these affected individuals also had dysplastic nevi (DN). An additional 15 family members had DN alone. Pedigrees fell into three groups: 1) hereditary melanoma alone with no associated DN, 2) hereditary melanoma with occasional DN-affected individuals, and 3) hereditary melanoma with DN. All families displayed an autosomal dominant pattern of inheritance. An analysis of the cosegregation of the cutaneous malignant melanoma/DN trait with eight polymorphic DNA markers on the short arm of chromosome 1, including the distally located DNA markers D1S47 and PND yielded a strongly negative probability of linkage. The putative gene for susceptibility to melanoma in these families was effectively excluded from this region of the short arm of chromosome 1. No evidence for linkage was found at any of the other chromosome 1 markers examined. These findings suggest that hereditary melanoma is heterogeneous in relation to the genetic basis and its association with the DNS.
Kefford
R F
RF
Department of Medicine, University of Sydney, Westmead Centre, NSW, Australia.
Salmon
J
J
Shaw
H M
HM
Donald
J A
JA
McCarthy
W H
WH
D000293:Adolescent; D000328:Adult; D002878:Chromosomes, Human, Pair 1; D004416:Dysplastic Nevus Syndrome / Q000150:complications* / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008545:Melanoma / Q000150:complications / Q000235:genetics*; D008875:Middle Aged; D009517:New South Wales; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length