CDC73 Gene Mutation In Parathyroid Adenomas And Atypical Adenomas

BackgroundPrimary hyperparathyroidism is an endocrine disorder caused by the excessive secretion of parathyroid hormone,which can lead to the disturbance of the electrolyte homeostasis and metabolism.The primary hyperparathyroidism could be caused by parathyroid adenoma,parathyroid hyperplasia and parathyroid carcinoma.Parathyroid carcinoma is a rare endocrine malignant tumor with poor prognosis.As a tumor suppressor,the inactivated mutation of CDC73 gene may lead to the decrease or loss of the expression of parafibromin protein,which plays an important role in the pathogenesis and prognosis of parathyroid carcinoma.The CDC73 status in parathyroid adenoma was still less known,especially in the special subtype such as large adenoma,cystic adenoma and atypical adenoma.ObjectiveTo analyze the mutations of CDC73 gene in parathyroid adenomas and atypical parathyroid adenomas.MethodsThe clinical characteristics of 86 patients diagnosed of large parathyroid adenoma,cystic adenoma and parathyroid atypical adenoma from June 2012 to June 2018 in PUMCH were reviewed.Genomic DNA was extracted from tumor tissues.The 17 exons and exons-intron boundaries of CDC73 was amplified with PCR(Polymerase Chain Reaction).The amplicon was then sequenced by Sanger sequencing to identify the mutations of CDC73 gene.ResultsBy Sanger sequencing,CDC73 gene mutations were found in 20.8%(5/24)parathyroid atypical adenomas,10.7%(3/28)large parathyroid adenomas,and 9.1%(1/11)parathyroid cystic adenomas,respectively.These mutation included frameshift mutation,missense mutation and splicing site mutation.CDC73 mutations were not found in 29 cases of parathyroid small adenomas.ConclusionCDC73 gene mutations were identified in a substantial proportion of atypical adenoma cases,large parathyroid adenomas,parathyroid cystic adenomas.The possibility of parathyroid malignant tumors should be considered in these subtype of patients.