Familial melanoma: Risk of disease as an inherited disorder

It is now widely appreciated that cancer may arise from multifactorial contributors both genetic and environmental. In approximately 10% of melanoma cases multiple family members are affected. Familial melanoma defines the occurrence of 3 or more melanomas in a family, 2 of which are found in first-degree relatives (Figure1). This suggests the existence of an inherited risk factor for melanoma in these families

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Figure 1 Family pedigree cartoon. Affected first-degree family members are indicated with a star

Melanoma is the most aggressive type of skin cancer (Figure 2). It is worth noting that there is only a partial understanding of the genetic basis of the disease. Scientific evidence showed that germline mutations in genes encoding for cell cycle checkpoint regulators (CDKN2A), telomere maintenance proteins (TERT, POT1) and several other genes (BAP1) cause hereditary melanoma. However approximately 60% of melanoma families need further elucidation.

Figure 2 Phenotypic characterisation of atypical nevus (melanoma)
Figure 2 Example of a melanoma

Whole genome sequencing of DNA from multiple Dutch familial melanoma cases has been performed to identify novel candidate variants responsible for the disease. Consequently, the overall aim of my PhD project is to clarify the melanoma-predisposing effects of newly identified gene variants using functional analysis.

My journey as a PhD candidate commenced in January 2016, yet I have already participated in a number of seminars and training conferences. I was also given the opportunity to attend this year’s annual GenoMEL meeting where I presented my ongoing work and discussed my future project plans with experts in the field. My future goals are to provide worthwhile data which could contribute to optimized medical and genetic surveillance of melanoma families.

Written by Eirini Christodoulou, ESR02