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@ARTICLE{Bailey:282336,
author = {P. Bailey and R. A. Ridgway and P. Cammareri and M.
Treanor-Taylor and U.-M. Bailey and C. Schoenherr and M.
Bone and D. Schreyer and K. Purdie and J. Thomson and W.
Rickaby and R. Jackstadt$^*$ and A. D. Campbell and E.
Dimonitsas and A. J. Stratigos and S. T. Arron and J. Wang
and K. Blyth and C. M. Proby and C. A. Harwood and O. J.
Sansom and I. M. Leigh and G. J. Inman},
title = {{D}river gene combinations dictate cutaneous squamous cell
carcinoma disease continuum progression.},
journal = {Nature Communications},
volume = {14},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2023-01720},
pages = {5211},
year = {2023},
abstract = {The molecular basis of disease progression from UV-induced
precancerous actinic keratosis (AK) to malignant invasive
cutaneous squamous cell carcinoma (cSCC) and potentially
lethal metastatic disease remains unclear. DNA sequencing
studies have revealed a massive mutational burden but have
yet to illuminate mechanisms of disease progression. Here we
perform RNAseq transcriptomic profiling of 110 patient
samples representing normal sun-exposed skin, AK, primary
and metastatic cSCC and reveal a disease continuum from a
differentiated to a progenitor-like state. This is
accompanied by the orchestrated suppression of master
regulators of epidermal differentiation, dynamic modulation
of the epidermal differentiation complex, remodelling of the
immune landscape and an increase in the preponderance of
tumour specific keratinocytes. Comparative systems analysis
of human cSCC coupled with the generation of genetically
engineered murine models reveal that combinatorial
sequential inactivation of the tumour suppressor genes
Tgfbr2, Trp53, and Notch1 coupled with activation of Ras
signalling progressively drives cSCC progression along a
differentiated to progenitor axis. Taken together we provide
a comprehensive map of the cSCC disease continuum and reveal
potentially actionable events that promote and accompany
disease progression.},
cin = {A014},
ddc = {500},
cid = {I:(DE-He78)A014-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37626054},
pmc = {pmc:PMC10457401},
doi = {10.1038/s41467-023-40822-9},
url = {https://inrepo02.dkfz.de/record/282336},
}