Targeted therapy of advanced parathyroid carcinoma guided by genomic and transcriptomic profiling

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragen


  • Maria-Veronica Teleanu - , Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • Carmina T Fuss - , Hospital de Basurto (Autor:in)
  • Nagarajan Paramasivam - , Computational Oncology Group (Autor:in)
  • Sebastian Pirmann - , Computational Oncology Group (Autor:in)
  • Andreas Mock - , Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • Christoph Terkamp - , Leibniz Universität Hannover (LUH) (Autor:in)
  • Stefan Kircher - , Universitätsklinikum Würzburg (Autor:in)
  • Laura-Sophie Landwehr - , Hospital de Basurto (Autor:in)
  • Christina Lenschow - , Hospital de Basurto (Autor:in)
  • Nicolas Schlegel - , Hospital de Basurto (Autor:in)
  • Albrecht Stenzinger - , Universitätsklinikum Heidelberg (Autor:in)
  • Arne Jahn - , Institut für Klinische Genetik, ERN GENTURIS, Institut für Klinische Genetik (Autor:in)
  • Martin Fassnacht - , Hospital de Basurto (Autor:in)
  • Hanno Glimm - , Deutsches Konsortium für Translationale Krebsforschung (Partner: DKTK, DKFZ), DRESDEN-concept, Medizinische Klinik und Poliklinik I, Nationales Centrum für Tumorerkrankungen (Partner: UKD, MFD, HZDR, DKFZ), Universitätsmedizin Mainz, Nationales Zentrum für Tumorerkrankungen (NCT) Dresden, Deutsches Krebsforschungszentrum (DKFZ), Universitätsklinikum Carl Gustav Carus Dresden, Helmholtz-Zentrum Dresden-Rossendorf (Autor:in)
  • Daniel Hübschmann - , Computational Oncology Group (Autor:in)
  • Stefan Fröhling - , Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • Matthias Kroiss - , Hospital de Basurto (Autor:in)


Parathyroid carcinoma (PC) is an ultra-rare malignancy with a high risk of recurrence after surgery. Tumour-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: (a) immune checkpoint inhibition with pembrolizumab based on high tumour mutational burden and a single-base substitution signature associated with APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) overactivation; (b) multi-receptor tyrosine kinase inhibition with lenvatinib due to overexpression of FGFR1 (Fibroblast Growth Factor Receptor 1) and RET (Ret Proto-Oncogene) and, (c) 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.


Seiten (von - bis)1343-1355
FachzeitschriftMolecular oncology
PublikationsstatusVeröffentlicht - Juli 2023

Externe IDs

PubMedCentral PMC10323885
Scopus 85152429909
WOS 000969302500001
Mendeley a8021f17-c909-35a5-9954-c94889518eb2


Ziele für nachhaltige Entwicklung


  • Humans, Parathyroid Neoplasms/drug therapy, Transcriptome/genetics, Mutation/genetics, Genomics/methods, Gene Expression Profiling/methods, Carcinoma/genetics, RNA sequencing, Mutational signature, Immune checkpoint inhibition, Whole-genome sequencing, Tyrosine kinase inhibition, Tumour mutational burden, whole-genome sequencing, tumour mutational burden, tyrosine kinase inhibition, mutational signature, immune checkpoint inhibition