Specific oncogene activation of the cell of origin in mucosal melanoma.

ABSTRACT: Mucosal melanoma (MM) is a deadly cancer derived from mucosal melanocytes. To test the consequences of MM genetics, we develop a zebrafish model in which all melanocytes experience CCND1 expression and loss of PTEN and TP53. Surprisingly, melanoma only develops from melanocytes lining internal organs, analogous to the location of patient MM. We find that zebrafish MMs have a unique chromatin landscape from cutaneous melanomas. Internal melanocytes are labeled using a MM-specific transcriptional enhancer. Normal zebrafish internal melanocytes share a gene expression signature with MMs. Patient and zebrafish MMs show increased migratory neural crest and decreased antigen presentation gene expression, consistent with the increased metastatic behavior and decreased immunotherapy sensitivity of

SUBMITTER: Babu S 

PROVIDER: S-EPMC12284105 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature