Show Notes
️ Episode 252: Keratinocytes to cSCC: genetic steps
In this episode of PaperCast Base by Base, we explore Single-cell and spatial multi-omic profiling maps the genetic and transcriptional changes from normal keratinocytes through actinic keratoses to invasive cutaneous squamous cell carcinoma
Study Highlights:
Single-cell genotyping of 137 keratinocytes revealed most cells have low mutation burdens (median 1.14 mut/Mb) while keratinocytes with TP53 or NOTCH1 mutations carry substantially higher burdens. Deep panel sequencing of 16 paired actinic keratoses and adjacent cSCCs showed TERT promoter and CDKN2A mutations arise in actinic keratoses and additional events such as ARID2 loss and MAPK pathway activation delineate progression to cSCC. Many actinic keratoses were genetically unrelated to their neighboring cSCCs, indicating independent clonal origins despite spatial proximity. Spatial transcriptomics exposed intratumoral heterogeneity and enrichment of immune checkpoint molecules at invasive fronts, implicating localized immune modulation.
Conclusion:
Keratinocyte transformation to cSCC follows a stereotyped sequence where TP53/NOTCH1-associated mutator phenotypes prime cells for acquisition of telomerase activation and cell-cycle defects in precursors, with SWI/SNF disruption and MAPK activation driving invasion alongside spatial immune evasion.
Music:
Enjoy the music based on this article at the end of the episode.
Reference:
Deivendran D, Chen L, Tandukar B, Bandari AK, Cruz-Pacheco N, Sharma H, Wang M, Xu A, Chen DB, George CD, Marty AL, Cho RJ, Cheng JB, Saylor D, Gerami P, Yeh I, Arron ST, Bastian BC, Shain AH. Genetic evolution of keratinocytes to cutaneous squamous cell carcinoma. Nature Communications. 2025;16:10663. https://doi.org/10.1038/s41467-025-65687-y
License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/
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On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics.
Episode link: https://basebybase.castos.com/episodes/keratinocytes-to-cscc-evolution
Episode Slug: keratinocytes-to-cscc-evolution
Keywords: keratinocytes, actinic keratosis, TP53, ARID2, spatial transcriptomics
