POT1 and multiple primary melanomas: the dermatological phenotype

Area of Science:

• Genetics
• Dermatology
• Oncology

Background:

• POT1 gene variants are linked to familial melanoma and multiple primary melanomas (MPMs).
• Previous POT1 research focused on associated malignancies, with limited dermatological phenotype descriptions.
• POT1 is the second most frequently reported gene in familial melanoma, after CDKN2A.

Purpose of the Study:

• To investigate the dermatological phenotype associated with POT1 gene variants.
• To characterize nevus counts and distribution in individuals carrying POT1 variants.

Main Methods:

• Genetic analysis identified 10 POT1 variants in 18 individuals with melanoma.
• Three-dimensional total body photography was used to assess nevus counts and distribution.
• Nevus counts in POT1 variant carriers were compared to a control population.

Main Results:

• Individuals with pathogenic POT1 variants had significantly higher total body nevus counts (≥2mm diameter).
• The majority of nevi were located on the back and lower limbs, regions with mild to moderate UV damage.
• Fewer nevi were observed in the head/neck region, despite severe UV damage in these areas.

Conclusions:

• Functional POT1 variants are associated with an increased number of nevi, especially those >5mm.
• The distribution of nevi appears independent of ultraviolet (UV) radiation damage.
• This study expands the known phenotype associated with POT1 variants beyond malignancy risk.