Journal article
Mutational patterns in a large cohort of parathyroid carcinomas
- Abstract:
-
Purpose: A lack of targeted therapies make parathyroid carcinoma, a diagnostically challenging malignancy, difficult to treat. The rarity of this tumor type necessitates international collaboration to collect a sizable sample set for study. Prior studies have revealed the importance of driver mutations in the CDC73 gene and identified several putative drivers/aberrant pathways including PI3K/mTOR activation and CCND1 (cyclin D1) amplification. In this study, we sought to better understand the prevalence of putative oncogenic drivers in parathyroid carcinoma.
Methods: We subjected an expanded cohort of 71 sporadic parathyroid carcinomas, fulfilling stringent WHO criteria, to next-generation DNA sequencing on a custom 16-gene targeted panel.
Results: One or more variant was detected in 44 tumors (62%) and 27 (38%) had no detectable variant. Consistent with earlier studies, we detected loss-of-function CDC73 mutations in 44% (31/70) of evaluable patients, including germline pathogenic variants in 9 patients (36 patients evaluable for somatic status as matched normal available). Notably, mutations in the PI3K/AKT/mTOR pathway were seen in 12.9% (9/70) of evaluable patients, providing further evidence of this as a key therapeutically actionable pathway in parathyroid carcinoma. Correlating genomic and clinical features revealed that patients harboring CDC73 mutations are more likely suffer from life threatening recurrent/metastatic parathyroid carcinoma (P = 0.024) than those without CDC73 variants.
Conclusions: This genomic characterization of a large parathyroid carcinoma cohort improves understanding of the genomic underpinnings of this rare malignancy, provides novel evidence for genotype-phenotype correlation with recurrent/metastatic disease, and may help to provide a rational basis for individualized treatments.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
Actions
Access Document
- Files:
-
-
(Preview, Version of record, pdf, 1.4MB, Terms of use)
-
- Publisher copy:
- 10.1007/s40618-026-02855-x
Authors
- Publisher:
- Springer
- Journal:
- Journal of Endocrinological Investigation More from this journal
- Publication date:
- 2026-03-25
- Acceptance date:
- 2026-03-01
- DOI:
- EISSN:
-
1720-8386
- ISSN:
-
0391-4097
- Language:
-
English
- Pubs id:
-
2385236
- Local pid:
-
pubs:2385236
- Deposit date:
-
2026-03-05
- ARK identifier:
Terms of use
- Copyright holder:
- Pandya et al.
- Copyright date:
- 2026
- Rights statement:
- Copyright © 2026, The Author(s). This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
If you are the owner of this record, you can report an update to it here: Report update to this record