Evidence map›Paper›PMID 41309580›Full record

ArticleNature communications2025

Genetic evolution of keratinocytes to cutaneous squamous cell carcinoma.

Bishal Tandukar, Delahny Deivendran, Limin Chen, Aravind K Bandari, Noel Cruz-Pacheco, Harsh Sharma, Meng Wang, Albert Xu, Daniel B Chen, Christopher D George and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. An Itch Receptor Drives Melanoma.bioRxiv : the preprint server for biology · 2026
    Article
  3. Article
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Bishal Tandukar *Department of Dermatology, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-9650-1664
Delahny Deivendran *Department of Dermatology, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-3046-2906
Limin ChenDepartment of Dermatology, University of California San Francisco, San Francisco, CA, USA.
Aravind K BandariDepartment of Dermatology, University of California San Francisco, San Francisco, CA, USA.
Noel Cruz-PachecoDepartment of Dermatology, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-8989-7093
Harsh SharmaDepartment of Dermatology, University of California San Francisco, San Francisco, CA, USA.
Meng WangDepartment of Dermatology, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-3209-1026
Albert XuDepartment of Dermatology, University of California San Francisco, San Francisco, CA, USA.
Daniel B ChenDepartment of Dermatology, University of California San Francisco, San Francisco, CA, USA.
Christopher D GeorgeDepartment of Dermatology, Erasmus MC, Rotterdam, Netherlands.ORCID http://orcid.org/0000-0003-2790-5443
Annika L MartyDepartment of Dermatology, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0009-0009-0554-131X
Raymond J ChoDepartment of Dermatology, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-6090-6603
Jeffrey B ChengDepartment of Dermatology, University of California San Francisco, San Francisco, CA, USA.
Drew SaylorDepartment of Dermatology, University of California San Francisco, San Francisco, CA, USA.
Pedram GeramiDepartment of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Iwei YehDepartment of Dermatology, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-3941-3561
Sarah T ArronPeninsula Dermatology, Burlingame, CA, USA.ORCID http://orcid.org/0000-0001-5669-0627
Boris C BastianDepartment of Dermatology, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-1836-6062
A Hunter ShainDepartment of Dermatology, University of California San Francisco, San Francisco, CA, USA. hunter.shain@ucsf.edu.ORCID http://orcid.org/0000-0002-2999-9706

Funding

Pre-cancer atlas of skin cancerU01CA294536 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BASTIAN, BORIS C., SHAIN, ALAN HUNTER · 2024 to 2025
$5.2M
The genomic landscape and evolution of cutaneous squamous cell carcinomaR01CA265786 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Alan Hunter Shain · 2022 to 2026
$2.1M
The mutational mechanisms shaping melanocytes in human skinR01AR080626 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Alan Hunter Shain · 2023 to 2026
$1.6M
Defining and treating genetic abnormalities in psoriasis/atopic dermatitis-overlap dermatosesR01AR084006 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Raymond Jaihyun Cho · 2025 to 2026
$1.2M
Investigating single-T cell atopic gene networks in Asian and Hispanic genetic backgroundsR56AR082484 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHO, RAYMOND JAIHYUN · 2024 to 2024
$344k
Melanoma Research Alliance (MRA) 988665Melanoma Research Alliance (MRA) Team Science AwardNCI NIH HHS R01 CA265786NCI NIH HHS U01 CA294536NIAMS NIH HHS R01 AR080626NIAMS NIH HHS R01 AR084006NIAMS NIH HHS R56 AR082484U.S. Department of Defense (United States Department of Defense) ME210014U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) AR080626
6 · The paper itself

Abstract

Cutaneous squamous cell carcinomas (cSCCs) arise from keratinocytes in the skin, but the molecular changes driving this transformation remain unclear. To better understand this process, we perform multi-omic profiling of keratinocytes, actinic keratoses, and cSCCs. Single-cell mutational analyses reveal that most keratinocytes have remarkably low mutation burdens; however, keratinocytes with TP53 or NOTCH1 mutations exhibit substantially higher burdens. These findings suggest that keratinocytes can withstand high dosages of cumulative ultraviolet radiation, but certain pathogenic mutations break these adaptive mechanisms, inducing a mutator phenotype. Mutational profiling of cSCCs adjacent to actinic keratoses reveals TERT promoter and CDKN2A mutations emerge in actinic keratoses, whereas additional mutations that inactivate ARID2 and activate the mitogen-activated protein kinase pathway delineate the transition to cSCC. Surprisingly, actinic keratoses are often not related to their neighboring cSCC. Spatial analyses reveal gene expression heterogeneity, including checkpoint molecule enrichment at invasive fronts, highlighting tumor and immune cell interactions.

Indexed as

Carcinoma, Squamous CellEvolution, MolecularKeratinocytesSkin NeoplasmsCyclin-Dependent Kinase Inhibitor p16Gene Expression Regulation, NeoplasticHumansKeratosis, ActinicMutationPromoter Regions, GeneticReceptor, Notch1Single-Cell AnalysisSkinTelomeraseTranscription FactorsTumor Suppressor Protein p53CDKN2A protein, humanCyclin-Dependent Kinase Inhibitor p16NOTCH1 protein, humanReceptor, Notch1TelomeraseTERT protein, humanTP53 protein, humanTranscription FactorsTumor Suppressor Protein p53

Identifiers

PMID41309580
PMCPMC12660313

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.