HLA complex and familial malignant melanoma

Abstract

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.

HLA DR4 Is Associated with the Development of Multiple Basal Cell Carcinomas and Malignant Melanoma

“…B8 110]. B27 [11], and B49 [12], In addition, there have been reports of HLA types and MM segregating together in some families [13,14]. This study found an association between HLA DR4 and the development of multiple BCCs and MM with a relative risk of 2.59.…”

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

“…Six families reported by Pellegris et al (1982), one reported by Hawkins et al (1981), 5 reported by Mueller-Eckhardt et al (1984) and 7 reported by Demenais et al (1984) were used in that portion of our analysis dealing with previously reported families.…”

“…Analysis of linkage between melanoma and HLA in high-risk families has been undertaken by 4 previous investigators to explore the possibility that a melanoma gene is located on chromosome 6. One series of 6 European 2-generation families (Pellegris et al, 1982) and another of 5 European multiplex families (Mueller-Eckhardt et al, 1984) were published but lod scores were not computed. A single 4-generation Australian family yielded a lod score of 1.25 with 10% recombination but extremely low estimates of penetrance were used in that study (Hawkins et al, 1981).…”

HLA in Familial Malignant Melanoma

“…They can be compared to those of two previous studies, concerning 7 French pedigrees [8] and a total of 22 families submitted for analysis to the 9th Histocompatibility Workshop [15], both series of families displaying the FAMMM syndrome. These two studies permitted us to rule out a close linkage between HLA and a single gene assumed to determine either precursor lesions or any of the clinical forms (precursor lesions and/or CMM), specially when the gene frequency is < 10 '.…”

“…The first observation of a possible linkage between FMM and HLA was made by Hawkins et al [6] with a maximum lod score of 1.25 at a recombination distance of 10 units. Then, Pellegris et al [7] have stud ied 6 families, and Demenais et al [8] ob served in an independent series of 7 pedigrees, a maximum lod score of 1.64 at a recombination fraction of 5% assuming low penetrance values, suggesting a possible linkage between HLA and FMM.…”