The genetic evolution of acral melanoma
Journal
Nature Communications
Series/Report No.
Nature Communications
Journal Volume
15
Journal Issue
1
ISSN
2041-1723
Date Issued
2024-07-21
Author(s)
Wang, Meng
Fukushima, Satoshi
Ramelyte, Egle
Cruz-Pacheco, Noel
Shi, Chenxu
Liu, Shanshan
Banik, Ishani
Aquino, Jamie D.
Sangueza Acosta, Martin
Levesque, Mitchell
Dummer, Reinhard
Liau, Jau-Yu
Shain, A. Hunter
Yeh, Iwei
Bastian, Boris C.
Abstract
Acral melanoma is an aggressive type of melanoma with unknown origins. It is the most common type of melanoma in individuals with dark skin and is notoriously challenging to treat. We examine exome sequencing data of 139 tissue samples, spanning different progression stages, from 37 patients. We find that 78.4% of the melanomas display clustered copy number transitions with focal amplifications, recurring predominantly on chromosomes 5, 11, 12, and 22. These complex genomic aberrations are typically shared across all progression stages of individual patients. TERT activating alterations also arise early, whereas MAP-kinase pathway mutations appear later, an inverted order compared to the canonical evolution. The punctuated formation of complex aberrations and early TERT activation suggest a unique mutational mechanism that initiates acral melanoma. The marked intratumoral heterogeneity, especially concerning MAP-kinase pathway mutations, may partly explain the limited success of therapies for this melanoma subtype.
SDGs
Publisher
Springer Science and Business Media LLC
Type
journal article