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@ARTICLE{Denisova:169023,
author = {E. Denisova$^*$ and D. Westphal and H. M. Surowy and F.
Meier and B. Hutter$^*$ and J. Reifenberger and A. Rütten
and A. Schulz and M. Sergon and M. Ziemer and B. Brors$^*$
and R. C. Betz and S. Redler},
title = {{W}hole-exome sequencing in eccrine porocarcinoma indicates
promising therapeutic strategies.},
journal = {Cancer gene therapy},
volume = {29},
number = {6},
issn = {1476-5500},
address = {New York, NY},
publisher = {Nature Publ. Group},
reportid = {DKFZ-2021-01191},
pages = {697-708},
year = {2022},
note = {#EA:B330# / 2022 Jun;29(6):697-708},
abstract = {Malignant sweat gland tumours are rare, with the most
common form being Eccrine porocarcinoma (EP). To investigate
the mutational landscape of EP, we performed whole-exome
sequencing (WES) on 14 formalin-fixed paraffin-embedded
samples of matched primary EP and healthy surrounding
tissue. Mutational profiling revealed a high overall median
mutation rate. This was attributed to signatures of
mutational processes related to ultraviolet (UV) exposure,
APOBEC enzyme dysregulation, and defective homologous
double-strand break repair. All of these processes cause
genomic instability and are implicated in carcinogenesis.
Recurrent driving somatic alterations were detected in the
EP candidate drivers TP53, FAT2, CACNA1S, and KMT2D. The
analyses also identified copy number alterations and
recurrent gains and losses in several chromosomal regions
including that containing BRCA2, as well as deleterious
alterations in multiple HRR components. In accordance with
this reduced or even a complete loss of BRCA2 protein
expression was detected in $50\%$ of the investigated EP
tumours. Our results implicate crucial oncogenic driver
pathways and suggest that defective homologous double-strand
break repair and the p53 pathway are involved in EP
aetiology. Targeting of the p53 axis and PARP inhibition,
and/or immunotherapy may represent promising treatment
strategies.},
cin = {B330 / HD01},
ddc = {610},
cid = {I:(DE-He78)B330-20160331 / I:(DE-He78)HD01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34045664},
doi = {10.1038/s41417-021-00347-z},
url = {https://inrepo02.dkfz.de/record/169023},
}