MITF E318K: A rare homozygous case with multiple primary melanoma

Area of Science:

• Genetics
• Dermatology
• Oncology

Background:

• The microphthalmia-associated transcription factor (MITF) gene plays a crucial role in melanocyte development and is implicated in melanoma risk.
• The E318K variant of MITF is a known moderate-risk factor for melanoma.
• Homozygosity for MITF variants is rare, with limited data on associated dermatological phenotypes and melanoma risk.

Observation:

• This report details the dermatological phenotype of a 32-year-old male with homozygous MITF E318K.
• The individual developed six primary melanomas starting at age 26.
• Three-dimensional total-body photography (3D-TBP) revealed a high nevus count (n=162) with varied pigmentation, predominantly on the back.
• Melanomas were primarily located on the back (n=5) and groin (n=1).

Findings:

• Melanoma location correlated with nevus density, particularly on the back, rather than the degree of sun damage.
• Most nevi, including large and atypical ones, were situated on the back, an area with mild sun damage.
• Conversely, areas with severe sun damage (head/neck, lower limbs) had a lower nevus count.
• The individual was also heterozygous for four other moderate-risk genetic variants.

Implications:

• This case suggests that nevus density, influenced by genetic factors like MITF E318K homozygosity, may be a critical determinant of melanoma location.
• Further research is needed to investigate if melanoma distribution in individuals with MITF E318K heterozygosity or other homozygous variants aligns with nevus density.
• Findings could inform personalized melanoma screening and surveillance strategies, focusing on high-nevus density areas.