% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Kuhn:277430,
author = {C. K. Kuhn and J. Meister and S. Kreft$^*$ and M. Stiller
and S.-H. Puppel and A. Zaremba$^*$ and B. Scheffler$^*$ and
V. Ullrich$^*$ and T. Schöneberg and D. Schadendorf$^*$ and
S. Horn$^*$},
title = {{TERT} expression is associated with metastasis from thin
primaries, exhausted {CD}4+ {T} cells in melanoma and with
{DNA} repair across cancer entities.},
journal = {PLOS ONE},
volume = {18},
number = {7},
issn = {1932-6203},
address = {San Francisco, California, US},
publisher = {PLOS},
reportid = {DKFZ-2023-01367},
pages = {e0281487 -},
year = {2023},
abstract = {Telomerase reverse transcriptase (TERT) promoter mutations
occur frequently in cancer, have been associated with
increased TERT expression and cell proliferation, and could
potentially influence therapeutic regimens for melanoma. As
the role of TERT expression in malignant melanoma and the
non-canonical functions of TERT remain understudied, we
aimed to extend the current knowledge on the impact of TERT
promoter mutations and expression alterations in tumor
progression by analyzing several highly annotated melanoma
cohorts. Using multivariate models, we found no consistent
association for TERT promoter mutations or TERT expression
with the survival rate in melanoma cohorts under immune
checkpoint inhibition. However, the presence of CD4+ T cells
increased with TERT expression and correlated with the
expression of exhaustion markers. While the frequency of
promoter mutations did not change with Breslow thickness,
TERT expression was increased in metastases arising from
thinner primaries. As single-cell RNA-sequencing (RNA-seq)
showed that TERT expression was associated with genes
involved in cell migration and dynamics of the extracellular
matrix, this suggests a role of TERT during invasion and
metastasis. Co-regulated genes found in several bulk tumors
and single-cell RNA-seq cohorts also indicated non-canonical
functions of TERT related to mitochondrial DNA stability and
nuclear DNA repair. This pattern was also evident in
glioblastoma and across other entities. Hence, our study
adds to the role of TERT expression in cancer metastasis and
potentially also immune resistance.},
keywords = {Humans / CD4-Positive T-Lymphocytes: pathology / Melanoma:
genetics / Melanoma: pathology / Skin Neoplasms: genetics /
Skin Neoplasms: pathology / Promoter Regions, Genetic /
Mutation / DNA Repair: genetics / Telomerase: genetics /
Telomerase (NLM Chemicals) / TERT protein, human (NLM
Chemicals)},
cin = {ED01},
ddc = {610},
cid = {I:(DE-He78)ED01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37418389},
pmc = {pmc:PMC10328343},
doi = {10.1371/journal.pone.0281487},
url = {https://inrepo02.dkfz.de/record/277430},
}