Transcriptional profiling reveals distinct classes of parathyroid tumors in PHPT.

Published

Journal Article

The clinical presentation of primary hyperparathyroidism (PHPT) varies widely, although the underlying mechanistic reasons for this disparity remain unknown. We recently reported that parathyroid tumors can be functionally segregated into two distinct groups on the basis of their relative responsiveness to ambient calcium, and that patients in these groups differ significantly in their likelihood of manifesting bone disability. To examine the molecular basis for this phenotypic variation in PHPT, we compared the global gene expression profiles of calcium-sensitive and calcium-resistant parathyroid tumors. RNAseq and proteomic analysis identified a candidate set of differentially expressed genes highly correlated with calcium-sensing capacity. Subsequent quantitative assessment of the expression levels of these genes in an independent cohort of parathyroid tumors confirmed that calcium-sensitive tumors cluster in a discrete transcriptional profile group. These data indicate that PHPT is not an etiologically monolithic disorder and suggest that divergent molecular mechanisms could drive the observed phenotypic differences in PHPT disease course, provenance, and outcome.

Full Text

Duke Authors

Cited Authors

  • Koh, J; Hogue, JA; Roman, SA; Scheri, RP; Fradin, H; Corcoran, DL; Sosa, JA

Published Date

  • April 2018

Published In

Volume / Issue

  • 25 / 4

Start / End Page

  • 407 - 420

PubMed ID

  • 29475894

Pubmed Central ID

  • 29475894

Electronic International Standard Serial Number (EISSN)

  • 1479-6821

Digital Object Identifier (DOI)

  • 10.1530/ERC-17-0470

Language

  • eng

Conference Location

  • England