Genomic Profiling Reveals Mutational Landscape in Parathyroid Carcinomas

Overview

Journal JCI Insight

Specialties Biomedical Engineering
General Medicine

Date 2017 Mar 30

PMID 28352668

Citations 51

Authors

Chetanya Pandya

Andrew V Uzilov

Justin Bellizzi

Chun Yee Lau

Aye S Moe

Maya Strahl

Wissam Hamou

Leah C Newman

Marc Y Fink

Yevgeniy Antipin

Willie Yu

Mark Stevenson

Branca M Cavaco

Bin T Teh

Rajesh V Thakker

Hans Morreau

Eric E Schadt

Robert Sebra

Shuyu D Li

Andrew Arnold

Rong Chen

Affiliations

Soon will be listed here.

Abstract

Parathyroid carcinoma (PC) is an extremely rare malignancy lacking effective therapeutic intervention. We generated and analyzed whole-exome sequencing data from 17 patients to identify somatic and germline genetic alterations. A panel of selected genes was sequenced in a 7-tumor expansion cohort. We show that 47% (8 of 17) of the tumors harbor somatic mutations in the tumor suppressor, with germline inactivating variants in 4 of the 8 patients. The PI3K/AKT/mTOR pathway was altered in 21% of the 24 cases, revealing a major oncogenic pathway in PC. We observed amplification in 29% of the 17 patients, and a previously unreported recurrent mutation in putative kinase . We identified the first sporadic PCs with somatic mutations in the Wnt canonical pathway, complementing previously described epigenetic mechanisms mediating Wnt activation. This is the largest genomic sequencing study of PC, and represents major progress toward a full molecular characterization of this rare malignancy to inform improved and individualized treatments.

Citing Articles

Variants in Parathyroid Carcinoma and Atypical Parathyroid Tumors.

Burke C, Bellizzi J, Costa-Guda J, Arnold A J Endocr Soc. 2025; 9(2):bvaf009.

PMID: 39885950 PMC: 11781200. DOI: 10.1210/jendso/bvaf009.

c.1155-3A>G is a pathogenic variant that causes aberrant splicing, disrupted parafibromin expression, and hyperparathyroidism-jaw tumor syndrome.

Needleman L, Chun N, Sitaraman S, Tan M, Sellmeyer D, Kebebew E JBMR Plus. 2024; 9(1):ziae149.

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Neuroendocrine neoplasms of head and neck, genitourinary and gynaecological systems, unknown primaries, parathyroid carcinomas and intrathyroid thymic neoplasms: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.

Hadoux J, Lamarca A, Grande E, Deandreis D, Kaltsas G, Janson E ESMO Open. 2024; 9(10):103664.

PMID: 39461777 PMC: 11549527. DOI: 10.1016/j.esmoop.2024.103664.

Efficacy of surufatinib in the treatment of advanced parathyroid carcinoma: A case report.

Yu Z, Zhou J, Li F, Xie X, Hu L, Chen L Heliyon. 2024; 10(17):e36656.

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A Comparative Genomic Analysis of Parathyroid Adenomas and Carcinomas Harboring Heterozygous Germline CDC73 Mutations.

Li Y, Simonds W, Chen H J Clin Endocrinol Metab. 2024; 110(2):429-440.

PMID: 39044678 PMC: 11747674. DOI: 10.1210/clinem/dgae506.

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