Dear Editor

Hyperparathyroidism (HPT) can arise from germline mutation of multiple endocrine neoplasia type 1 (MEN1), CASR, or HRPT (HRPT1; Marx 2011). Recent studies also suggested that germline mutation of several cyclin-dependent kinase inhibitors (CDKIs) is an uncommon cause of HPT (Pellegata et al. 2006, Agarwal et al. 2009). A gene that predisposes to tumor via germline mutation may also predispose to similar tumor by somatic mutation; in fact, the MEN1 gene is mutated in about 30% of sporadic parathyroid tumors (Marx 2011). Screening a small number of sporadic parathyroid tumors by others, using whole exome sequencing analysis, did not show any CDKI gene mutation (Cromer et al. 2012, Newey et al. 2012). In a recent study, all seven CDKI genes were sequenced in 81 sporadic parathyroid adenomas. There were five novel DNA missense changes in p15, p18, and p21. Three to four of these were also in the germline, and none of the five were unequivocally a pathological mutation, such as a truncation change (Costa-Guda et al. 2013). We further evaluated whether some cases of sporadic parathyroid adenoma are caused by somatic mutation in CDKI genes.

We evaluated tumors from 42 patients, who underwent parathyroid surgery at NIH. Each patient had a postoperative diagnosis of sporadic parathyroid adenoma. Each patient gave written informed consent to a protocol that had been approved by the NIDDK Institutional Review Board. See Supplementary Materials and methods, see section on supplementary data given at the end of this article.

In 42 sporadic parathyroid adenomas, we found 15 SNPS plus one deletion and one …