Novel loss-of-function variant in DENND5A impedes melanosomal cargo transport and predisposes to familial cutaneous melanoma.

ABSTRACT:

Purpose

More than half of the familial cutaneous melanomas have unknown genetic predisposition. This study aims at characterizing a novel melanoma susceptibility gene.

Methods

We performed exome and targeted sequencing in melanoma-prone families without any known melanoma susceptibility genes. We analyzed the expression of candidate gene DENND5A in melanoma samples in relation to pigmentation and UV signature. Functional studies were carried out using microscopic approaches and zebrafish model.

Results

We identified a novel DENND5A truncating variant that segregated with melanoma in a Swedish family and 2 additional rare DENND5A variants, 1 of which segregated with the disease in an American family. We found that DENND5A is significantly enriched in pigmented melanoma

SUBMITTER: Yang M 

PROVIDER: S-EPMC10617683 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature