Hereditary malignant melanoma is not linked to the hla complex on chromosome 6

Abstract

Detailed HLA typing was performed in 11 families with hereditary cutaneous malignant melanoma (CMM) and dysplastic nevi to determine if the melanoma susceptibility locus was genetically linked to the major histocompatibility complex. Previously published data from 19 other families were re-analyzed in the same manner. When data from all 30 families were pooled and CMM was defined as the disease trait, the hypothesis of linkage was rejected for all values of recombination (theta) less than 40%. Data on family members' status regarding dysplastic nevi (DN), a well-characterized precursor of hereditary CMM, were available for our 11 families and 7 previously-reported families. Linkage analysis between the combined CMM/DN trait and HLA provided strong evidence against this hypothesis. Significant heterogeneity was observed when various sub-groups of families were compared; these data suggested that preferential reporting of positive linkage findings and misclassification of study subjects' CMM susceptibility status may have contributed to previous beliefs that the hereditary melanoma gene was linked to HLA. When our data are combined with previously-published information, we conclude that there is strong evidence against linkage of a CMM/DN gene with the major histocompatibility complex.

Identification of five chromosomal regions involved in predisposition to melanoma by genome‐wide scan in the MeLiM swine model

“…Although the MeLiM alleles were not informative in this area, we found a significant association between melanoma and one large Duroc SLA haplotype, and the linkage tests reached significance level. These results are in agreement with those reported for humans, for whom a suggestive linkage with the human leukocyte antigen (HLA) complex (LD = 1.6) has been reported in 2 separate studies,68, 69 although the results of a third study of 30 families worldwide excluded the linkage of melanoma to HLA 70. Moreover, in Sinclair swine, the SLA international haplotype H1071 was found to increase the penetrance of the unknown major initiator locus 35.…”

HLA class II polymorphisms in Spanish melanoma patients: homozygosity for HLA-DQA1 locus can be a potential melanoma risk factor

“…Linkage analysis in familial melanoma has also produced contradictory results. So, whereas evidence suggesting linkage with a region included in the HLA complex in chromosome arm 6p was described by some authors, 12 others found no linkage of hereditary malignant melanoma to the HLA region 13,14 …”

The Dutch FAMMM family material: Clinical and genetic data

“…Most investigators studying pedigrees with the FAMMM syn drome came to the conclusion that the condition shows a domi nant pattern of inheritance with on the average 40-50% of children of affected individuals being gene carriers themselves (Lynch et al, 1983;Greene et al, 1983;Bale et al, 1985). However, arguments against autosomal dominant inheritance were presented by Happle and coworkers, who suggested poly genic inheritance (Happle et al, 1982;Traupe et al, 1989).…”