Familial malignant melanoma - overview

Abstract

Approximately 3-15% of all malignant melanomas (MM) are familial cases. MM is a highly heterogeneous tumour type from a genetic perspective. Pedigrees with disease confined to a single generation of siblings or MM occurring among second- or third-degree relatives suggest multifactorial polygenic inheritance. However, not infrequently, within large families aggregations of MM are consistent with autosomal dominant inheritance, suggesting a hereditary syndrome caused by germline alterations of a single gene. Several different genes are involved in the development of MM. However, even when taken together they are responsible for less than 20% of all MM cases. It is thus necessary to perform association studies focused on genetic markers that could be used in identifying patients with a high risk of MM. Evaluation of aggregations of MM and other malignancies, like breast cancer, could be essential in identifying relatives of MM probands being at high risk of developing malignancies other than MM. The ultimate goal is to apply in these cases prevention recommendations and surveillance protocols to reduce the disease risk.

Figure 1

Pedigree of a family with melanoma diagnosed among first-degree relatives registered in our center.

Figure 2

Pedigree of a family with familial aggregations with MM and malignancies of different site of origin.