Comprehensive Profiling of Acral Lentiginous Melanoma Reveals Downregulated Immune Activation Compared to Cutaneous Melanoma.

ABSTRACT: Acral lentiginous melanoma (ALM) is a rare and insufficiently understood subtype of melanoma lacking in effective treatment options. Recent work has demonstrated that the response of ALM to immune checkpoint blockade is inferior to that of cutaneous melanoma (CM). Here we performed bulk genomic and transcriptomic sequencing of tumor tissue from 28 ALM and 5692 CM cases. Similar to prior studies, ALM was associated with a significantly lower incidence of point mutations, including in the TERT promoter and BRAF, but increased numbers of gene amplifications, notably of CCND1, HMGA2, and MDM2. Reactome pathway analysis revealed enhancement of keratinization and PI3K/AKT signaling pathways. Overall immunogenicity was decreased in ALM, which possessed lower IFNγ (p < 0.001) and T-cell inflammato

SUBMITTER: Wang SJ 

PROVIDER: S-EPMC12099029 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature