Genetic Alteration Profiles and Clinicopathological Associations in Atypical Parathyroid Adenoma

Abstract

Genomic aberrations associated with atypical parathyroid adenoma (AA) are poorly understood. Thus, herein, we sought to expand our current understanding of the molecular basis of atypical parathyroid adenomas. We analyzed 134 samples that had been surgically obtained from parathyroid tumors, including parathyroid carcinomas, atypical parathyroid adenomas, and parathyroid adenomas. The tumors were harvested from formalin-fixed, paraffin-embedded tissues. Fifteen tumor-related genes from recently published genome sequencing data were subjected to targeted sequencing analysis, and an average sequencing depth of 500x was achieved. Sixteen (16/50, 32%) AA tumors harbored at least one of the following genomic alterations: CDC73 (12, 24%), EZH2 (4, 8%), HIC1 (1, 2%), and CDKN2A (1, 2%). Our study identified, for the first time, a relatively high frequency of genomic alterations in patients with AA in a Chinese population. This suggests that AA arises de novo, rather than developing from a parathyroid adenoma. Altogether, these findings will improve our understanding of the malignant potential of parathyroid tumors at the molecular level.

Somatic and Germline Mutations in Atypical Parathyroid Tumors

“…They found mutations in EZH2 in 11% of the samples and MEN1 in 9%, although 60% of the samples had mutations in CDC73, suggestive of PCs rather than APTs. 1,5 The mutational background of APTs in the present study is consistent with prior studies 3,4 of benign PAs. In total, 22% of the patients in the present study had mutations in MEN1, which occur in 20% to 40% of benign PAs.…”

“…To our knowledge, this case series represents the largest report to date of genetic mutations in atypical parathyroid adenomas using broad NGS. Previously, a group from China sequenced 50 APT patient samples; however, they included only 15 genes in their panel. They found mutations in EZH2 in 11% of the samples and MEN1 in 9%, although 60% of the samples had mutations in CDC73 , suggestive of PCs rather than APTs …”

“…Previously, a group from China sequenced 50 APT patient samples; however, they included only 15 genes in their panel. They found mutations in EZH2 in 11% of the samples and MEN1 in 9%, although 60% of the samples had mutations in CDC73 , suggestive of PCs rather than APTs …”

Parathyroid Crisis as Presentation of Atypical Parathyroid Adenoma: Two Diagnostically Challenging Cases

“…[ 8 ] The pathophysiological mechanisms of APA are unclear, but it has been proposed that it may share molecular mechanisms with PC. [ 9 ] APA has higher rates of symptomatic hypercalcemia and fragility fracture, higher preoperative serum calcium, higher 24-hr urinary calcium and higher pre and postoperative PTH than typical adenoma. [ 4 ] The clinical and biochemical differences between APA and PC are nil, making differential diagnosis difficult without histopathological analysis.…”

Patterns and Predictors of Cervical Lymph Node Metastasis in Parathyroid Carcinoma

“…Most of the parafibromin and Ki67 immunohistochemical (IHC) staining results and CDC73 mutation status data were collected from previous studies at our institute [ 24 , 25 , 26 , 27 ]. Some of the IHC results and CDC73 sequencing were supplemented according to our previous studies mentioned above.…”