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@ARTICLE{Teleanu:271249,
author = {M.-V. Teleanu$^*$ and C. T. Fuss and N. Paramasivam and S.
Pirmann and A. Mock$^*$ and C. Terkamp and S. Kircher and
L.-S. Landwehr and C. Lenschow and N. Schlegel and A.
Stenzinger and A. Jahn and M. Fassnacht and H. Glimm$^*$ and
D. Hübschmann and S. Fröhling$^*$ and M. Kroiss},
title = {{T}argeted therapy of advanced parathyroid carcinoma guided
by genomic and transcriptomic profiling.},
journal = {Molecular oncology},
volume = {17},
number = {7},
issn = {1574-7891},
address = {Hoboken, NJ},
publisher = {John Wiley $\&$ Sons, Inc.},
reportid = {DKFZ-2023-00381},
pages = {1343-1355},
year = {2023},
note = {#EA:B340#LA:B340# / 2023 Jul;17(7):1343-1355},
abstract = {Parathyroid carcinoma (PC) is an ultra-rare malignancy with
a high risk of recurrence after surgery. Tumor-directed
systemic treatments for PC are not established. We used
whole-genome and RNA sequencing in four patients with
advanced PC to identify molecular alterations that could
guide clinical management. In two cases, the genomic and
transcriptomic profiles provided targets for experimental
therapies that resulted in biochemical response and
prolonged disease stabilization: (i) immune checkpoint
inhibition with pembrolizumab based on high tumor mutational
burden and a single-base substitution signature associated
with APOBEC (apolipoprotein B mRNA editing enzyme, catalytic
polypeptide-like) overactivation; (ii) multi-receptor
tyrosine kinase inhibition with lenvatinib due to
overexpression of FGFR1 (Fibroblast Growth Factor Receptor
1) and RET (Ret Proto-Oncogene) and, later in the course of
the disease, PARP (Poly(ADP-Ribose) Polymerase) inhibition
with olaparib prompted by signs of defective homologous
recombination DNA repair. In addition, our data provided new
insights into the molecular landscape of PC with respect to
the genome-wide footprints of specific mutational processes
and pathogenic germline alterations. These data underscore
the potential of comprehensive molecular analyses to improve
care for patients with ultra-rare cancers based on insight
into disease biology.},
keywords = {RNA sequencing (Other) / Whole-genome sequencing (Other) /
immune checkpoint inhibition (Other) / mutational signature
(Other) / tumor mutational burden (Other) / tyrosine kinase
inhibition (Other)},
cin = {B340 / DD01 / HD01 / B280},
ddc = {610},
cid = {I:(DE-He78)B340-20160331 / I:(DE-He78)DD01-20160331 /
I:(DE-He78)HD01-20160331 / I:(DE-He78)B280-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36808802},
doi = {10.1002/1878-0261.13398},
url = {https://inrepo02.dkfz.de/record/271249},
}