Exploration of the mutational landscape of cutaneous leiomyoma confirms FH as a driver gene and identifies targeting purine metabolism as a potential therapeutic strategy
(2025) British Journal of Dermatology — Vol. 192, n° 3, p. 551-553 (2025)
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- Authors
van der Weyden, Louise 
Del Castillo Velasco-Herrera, Martin Cheema, Saamin Adams, David J
- Abstract
- To comprehensively explore the mutational landscape of cutaneous leiomyoma (cLM) and identify candidate driver events, we performed a retrospective, multi-institutional, whole-exome sequencing and RNA sequencing study. We confirmed that a large proportion of patients with cLM have germline variants and additionally showed that somatic alteration of also drives cLM, with biallelic inactivation of being a frequent event. Treatment of -proficient and -deficient cell lines with the purine antagonist and chemotherapeutic agent, mercaptopurine, significantly decreased growth/colony formation; however, the addition of nucleosides was able to rescue only the -proficient cells, suggesting that purine metabolism is a targetable vulnerability for -deficient cLMs.
- Affiliations
Wellcome Sanger Institute Experimental Cancer Genetics
Citations
van der Weyden, L., Del Castillo Velasco-Herrera, M., Cheema, S., Wong, K., Boccacino, J. M., Vermes, I., Offord, V., Droop, A., Jones, D. R. A., Anderson, E., Hardy, C., de Saint Aubain, N., Ferguson, P. M., Mogler, C., Rajan, N., Frew, D., Harms, P. W., Billings, S. D., Schatton, D., et al. (2025). Exploration of the mutational landscape of cutaneous leiomyoma confirms FH as a driver gene and identifies targeting purine metabolism as a potential therapeutic strategy. British Journal of Dermatology, 192(3), 551-553. https://doi.org/10.1093/bjd/ljae432 (Original work published 2025)