Journal Article

DKFZ-2023-00381

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Targeted therapy of advanced parathyroid carcinoma guided by genomic and transcriptomic profiling.

Teleanu, M.-V. (First author)DKFZ* ; Fuss, C. T. ; Paramasivam, N. ; Pirmann, S. ; Mock, A.DKFZ* ; Terkamp, C. ; Kircher, S. ; Landwehr, L.-S. ; Lenschow, C. ; Schlegel, N. ; Stenzinger, A. ; Jahn, A. ; Fassnacht, M. ; Glimm, H.DKFZ* ; Hübschmann, D. ; Fröhling, S. (Last author)DKFZ* ; Kroiss, M.

2023
John Wiley & Sons, Inc. Hoboken, NJ

This record in other databases:  

Please use a persistent id in citations: doi:10.1002/1878-0261.13398

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.

Keyword(s): RNA sequencing ; Whole-genome sequencing ; immune checkpoint inhibition ; mutational signature ; tumor mutational burden ; tyrosine kinase inhibition

Note: #EA:B340#LA:B340# / 2023 Jul;17(7):1343-1355

---

Contributing Institute(s):

1. Translationale Medizinische Onkologie (B340)
2. DKTK Koordinierungsstelle Dresden (DD01)
3. DKTK HD zentral (HD01)
4. B280 Translationale funktionelle Krebsgenomik (B280)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2023

---

Database coverage:
; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---