Discovery of germline and somatic mutations in apparently sporadic parathyroid tumours

Abstract

Abstract Background To discriminate between sporadic and hereditary parathyroid tumours and characterize multiple endocrine neoplasia type 1 (MEN1) somatic mutations, MEN1 gene mutations were examined in patients with apparently sporadic parathyroid tumours. Methods DNA was extracted from fresh frozen parathyroid tumour specimens from 112 patients, as well as from peripheral blood leucocytes (PBL) from 60 of the 112 patients. Sequencing was performed to examine exons 2–10 of the MEN1 gene for mutations. In addition, exons 10 and 11 of the RET gene were sequenced. Results MEN1 mutations were found in 25 (22 per cent) of the 112 patients. Two patients had two simultaneous point-mutations. A total of 27 mutations were characterized, 24 of which have not been reported previously. There were seven nonsense mutations, ten frameshift mutations, two splice-site deletions, five missense mutations and three in-frame mutations. Nineteen mutations resulted in truncation of menin protein. Germline MEN1 mutations were found in three of 60 patients who had no family history of endocrine tumours associated with MEN1, and these patients were identified as MEN1 gene family probands. No somatic or germline RET exon 10 and 11 mutations were found in this series. Conclusion These findings suggest that MEN1 gene mutation may be associated not only with endocrine tumours of affected patients with MEN1 but also with sporadic parathyroid tumours. MEN1 gene analysis can distinguish inheritable from non-inheritable parathyroid tumours and MEN1 gene evaluation of patients with apparently sporadic parathyroid tumours is necessary before parathyroid surgery.