Uncovering minimal pathways in melanoma initiation

Hui Xiao, Jessica Shiu, Chi-Fen Chen, Jie Wu, Peijie Zhou, Sahil S. Telang, Rolando Ruiz-Vega, Robert A. Edwards, Qing Nie, Arthur D. Lander and Anand K. Ganesan ()
Additional contact information
Hui Xiao: University of California
Jessica Shiu: University of California
Chi-Fen Chen: University of California
Jie Wu: University of California
Peijie Zhou: University of California
Sahil S. Telang: University of California
Rolando Ruiz-Vega: University of California
Robert A. Edwards: University of California
Qing Nie: University of California
Arthur D. Lander: University of California
Anand K. Ganesan: University of California

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract Melanomas are genetically heterogeneous, displaying mitogen-activated protein kinase mutations and homozygous loss of tumor suppressor genes. Mouse models combining such mutations produce fast-growing tumors. In contrast, rare, slow-growing tumors arise in mice combining Braf activation with heterozygous loss of Pten. Here we show that similar tumors can arise in albino mice bearing only a Braf mutation. Incidence kinetics suggest a stochastic event underlies tumorigenesis in tumors that arise with only a Braf mutation, yet de novo mutations or structural variants that could explain the incidence of most tumors could not be found. Single-cell transcriptomics of tumors identify a cell type resembling “neural crest-like” cells in human and mouse melanomas. These exist in normal mouse skin, expand upon Braf activation, and persist through serial transplantation; analyses of gene expression suggest they serve as precursors of malignant cells. This state may serve as an intermediate on a slow path to malignancy that may provide a diagnostically and therapeutically important source of cellular heterogeneity.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-60742-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60742-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-60742-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().