TY  - JOUR
AU  - Teleanu, Maria-Veronica
AU  - Fuss, Carmina T
AU  - Paramasivam, Nagarajan
AU  - Pirmann, Sebastian
AU  - Mock, Andreas
AU  - Terkamp, Christoph
AU  - Kircher, Stefan
AU  - Landwehr, Laura-Sophie
AU  - Lenschow, Christina
AU  - Schlegel, Nicolas
AU  - Stenzinger, Albrecht
AU  - Jahn, Arne
AU  - Fassnacht, Martin
AU  - Glimm, Hanno
AU  - Hübschmann, Daniel
AU  - Fröhling, Stefan
AU  - Kroiss, Matthias
TI  - Targeted therapy of advanced parathyroid carcinoma guided by genomic and transcriptomic profiling.
JO  - Molecular oncology
VL  - 17
IS  - 7
SN  - 1574-7891
CY  - Hoboken, NJ
PB  - John Wiley & Sons, Inc.
M1  - DKFZ-2023-00381
SP  - 1343-1355
PY  - 2023
N1  - #EA:B340#LA:B340# / 2023 Jul;17(7):1343-1355
AB  - 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.
KW  - RNA sequencing (Other)
KW  - Whole-genome sequencing (Other)
KW  - immune checkpoint inhibition (Other)
KW  - mutational signature (Other)
KW  - tumor mutational burden (Other)
KW  - tyrosine kinase inhibition (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:36808802
DO  - DOI:10.1002/1878-0261.13398
UR  - https://inrepo02.dkfz.de/record/271249
ER  -