# Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma

Source: https://onco.cc/key-papers/paper-shattuck-n-engl-j-med/  
OnCo record `paper-shattuck-n-engl-j-med` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Paper cited by one cancer page, indexed on Europe PMC as PubMed record 14585940 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.

## Summary

Background: We looked for mutations of the HRPT2 gene, which encodes the parafibromin protein, in sporadic parathyroid carcinoma because germ-line inactivating HRPT2 mutations have been found in a type of familial hyperparathyroidism--hyperparathyroidism-jaw tumor (HPT-JT) syndrome--that carries an increased risk of parathyroid cancer.

Methods: We directly sequenced the full coding and flanking splice-junctional regions of the HRPT2 gene in 21 parathyroid carcinomas from 15 patients who had no known family history of primary hyperparathyroidism or the HPT-JT syndrome at presentation. We also sought to confirm the somatic nature of the identified mutations and tested the carcinomas for tumor-specific loss of heterozygosity at HRPT2.

Results: Parathyroid carcinomas from 10 of the 15 patients had HRPT2 mutations, all of which were predicted to inactivate the encoded parafibromin protein. Two distinct HRPT2 mutations were found in tumors from five patients, and biallelic inactivation as a result of a mutation and loss of heterozygosity was found in one tumor. At least one HRPT2 mutation was demonstrably somatic in carcinomas from six patients. Unexpectedly, HRPT2 mutations in the parathyroid carcinomas of three patients were identified as germ-line mutations.

Conclusions: Sporadic parathyroid carcinomas frequently have HRPT2 mutations that are likely to be of pathogenetic importance. Certain patients with apparently sporadic parathyroid carcinoma carry germ-line mutations in HRPT2 and may have the HPT-JT syndrome or a phenotypic variant.

Indexed on Europe PMC as PubMed record 14585940 (DOI 10.1056/nejmoa031237). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: New England Journal of Medicine
- Year: 2003
- DOI: 10.1056/nejmoa031237
- Authors: Shattuck TM, Välimäki S, Obara T, et al.
- What it means: One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
- Caveats: Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper.

## Sources

- N Engl J Med 2003: https://doi.org/10.1056/nejmoa031237
- PubMed: https://pubmed.ncbi.nlm.nih.gov/14585940/
- Europe PMC: https://europepmc.org/article/MED/14585940

## Connected records

- cancers: [Parathyroid carcinoma](https://onco.cc/cancers/parathyroid-carcinoma/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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