UK study findings indicate that mutations in the gene that encodes the parafibromin protein, called HRPT2, may play a role in the development of sporadic parathyroid carcinomas.
Researchers writing in the journal Clinical Endocrinology say that the HRPT2 gene is a strong parathyroid tumor suppressor, and, in the absence of a fully functioning HRPT2 gene, sporadic parathyroid carcinoma is likely to develop.
Speaking to Medwire News, lead author Rajesh Thakker, from the University of Oxford and the Churchill Hospital, said that delineation of the role of the HRPT2 gene is an "important issue."
He explained that while the team found that HRPT2 mutations are related to the development of sporadic parathyroid carcinomas, the lack of these mutations in patients with benign parathyroid tumors is also an important finding.
"Clinicians should be aware that if mutations of the HRPT2 gene are not identified in patients, then you are more likely to get a benign than a malignant parathyroid tumor," he said.
The research team assessed 31 parathyroid tumors for somatic mutations of the HRPT2 gene. These tumors were taken from four patients with hyperparathyroidism-jaw tumor (HRP-JT) syndrome or familial isolated hyperparathyroidism (FIHP), and the remainder were collected from individuals with nonfamilial, benign, sporadic hyperparathyroidism.
Three heterozygous germline HRPT2 mutations were identified; two in HRP-JTs and one in an FIHP patient. Of these, there was a single 1-bp duplication, as well as one nonsense and one missense mutation.
Interestingly, the 27 sporadic benign parathyroid tumors did not show any HRPT2 mutations. Instead, six HRPT2 polymorphisms with allele frequencies that ranged from 2-15% were identified in these tumors.
Thakker noted that the findings particularly indicate that, "in patients with parathyroid tumors arriving at an early age (<35 years), a genetic predisposition to parathyroid disease is implied."
Moreover, future study of the role of the HRPT2 gene in a variety of tumors other than those of the parathyroid gland is especially important, said Thakker.
He explained: "Mutations in the HRPT2 gene lead to the development of parathyroid tumors, which may be cancerous, together with tumors in the kidneys, uterus, and bone."