Whole-genome landscapes of major melanoma subtypes
Whole-genome sequencing of 183 melanomas showed that acral and mucosal melanomas have far fewer mutations than sun-exposed skin melanomas but many more structural rearrangements, confirming they are biologically different diseases.
Overview
Whole-genome sequencing of 183 melanomas including cutaneous, acral and mucosal subtypes, characterising mutation burden, ultraviolet signatures, structural variants, telomerase promoter alterations and driver genes.
Cutaneous melanomas carried a high ultraviolet-signature mutation load, whereas acral and mucosal melanomas had low point-mutation burden, frequent structural variants and amplifications (including KIT, CDK4 and CCND1), and different driver patterns.
- Acral and mucosal melanomas: low mutation burden, high structural variant load.
- Frequent amplifications of KIT, CDK4 and CCND1 in non-sun-exposed subtypes.
The lower response of acral and mucosal melanoma to immunotherapy and the interest in KIT and CDK4/6 inhibitors for these subtypes follow from this genomic picture.
- Relatively small numbers of acral and mucosal tumours.
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