Evidence for linkage between HLA and malignant melanoma

CDKN2A (9p21) and CDK4 (12q13) have been identified as melanoma susceptibility genes in certain familial melanoma (FM) kindreds. There remain other FM families, however, for which there is little or no evidence for linkage of melanoma to these loci. Other loci may be involved in susceptibility to this malignancy. Chromosome 6 is deleted or rearranged in 66% of melanomas and has been targeted by several studies in an attempt to identify chromosomal regions associated with initiation or progression of melanoma. Previous studies of familial melanoma and chromosome arm 6p reported evidence suggestive of linkage for markers flanking the HLA complex. We have carried out genetic linkage analysis in 14 Australian familial melanoma kindreds using 16 short tandem repeat polymorphism (STRP) markers spanning 6p23–6q27. Analysis by maximum likelihood and non‐parametric (affected pedigree member) techniques showed no evidence of linkage of melanoma in this family set to chromosome 6 (two‐point Zmax = 0.5 at θ=0.2 for D6S285 ). Lod scores >1.0 were obtained for the loci D6S285, D6S105, D6S265, D6S292, and D6S311 in three individual kindreds but these were insufficiently strong for formal heterogeneity testing to confirm that a chromosome 6‐linked subset of families exists. These data imply little or no role for a major chromosome 6 melanoma susceptibility locus; however the possibility of such a locus remains open and warrants further investigation. Genes Chromosom. Cancer 19:241–249, 1997. © 1997 Wiley‐Liss, Inc.

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Linkage analysis of familial melanoma and chromosome 6 in 14 Australian kindreds

Holland

Beaton

Kefford

et al. 1997

Genes Chromosom. Cancer

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Familial aggregation of melanoma, basal cell carcinoma, and gastric adenocarcinoma

Weston

Grufferman

Kostyu

et al. 1986

Cancer

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A family with four cases of melanoma, seven cases of basal cell carcinoma, and two cases of gastric adenocarcinoma, is described. The proband, who had three different primary tumors, died of gastric cancer, as did his father. Four of the proband's six siblings were affected with melanoma or basal cell cancer, as were two of his three children. Both daughters of one melanoma patient developed basal cell cancers. No spouses were affected, the cases were widely separated in time and place, and no unusual exposures were reported. HLA analysis of affected and unaffected first-degree relatives showed no association with antigens previously described in familial melanoma or segregation with a specific HLA haplotype. Although there was no association with HLA phenotype, these results suggest that melanoma, basal cell carcinoma, and gastric adenocarcinoma can be inherited in an autosomally dominant pattern similar to other familial tumor syndromes.

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HLA complex and familial malignant melanoma

Pellegris

Illeni

Rovini

et al. 1982

Intl Journal of Cancer

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Six families with familial malignant melanoma (FMM) were HLA-A, -B, and -C typed to ascertain whether or not FMM would segregate with the HLA complex. The HLA-B12 antigen was present in five of the six families. In three families the HLA-FMM linkage could be analyzed: linkage was possible in two but not in the third. These findings suggested that two types of FMM may exist: a more frequent type (five cases) that apparently segregates with the HLA complex and another (one case) that does not segregate with the HLA complex. Moreover, a factor included in the HLA region or another factor linked to it may have played an important role, in five of the six families, in FMM pathogenesis, whereas in the sixth family its role may have been performed by some other factor. These findings are consistent with the hypothesis of two complementary factors (one of which was included in the HLA complex) for the promotion of FMM with dominant inheritance and high penetrance.

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Evidence for linkage between HLA and malignant melanoma

Cited by 29 publications

References 5 publications

Linkage analysis of familial melanoma and chromosome 6 in 14 Australian kindreds

Linkage analysis of familial melanoma and chromosome 6 in 14 Australian kindreds

Familial aggregation of melanoma, basal cell carcinoma, and gastric adenocarcinoma

HLA complex and familial malignant melanoma

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