title: Novel HRPT2/CDC73 gene mutations and loss of expression of parafibromin in Chinese patients with clinically sporadic parathyroid carcinomas.
abstract: OBJECTIVE
  It is widely recognized that the diagnosis of parathyroid carcinoma (PC) is often difficult because of the overlap of characteristics between malignant and benign parathyroid tumors, especially at an early stage. Based on the identification of tumor suppressor gene HRPT2/CDC73 and its association with hereditary and sporadic PC, screening of gene mutations and detection of parafibromin immunoreactivity have been suggested as diagnostic instruments of PC in Whites. There is little information about HRPT2/CDC73 mutations and its corresponding protein expression in patients with sporadic PC in Chinese population, and the long-term follow-up data is scarce.
  
  
  METHODS
  Paraffin-embedded tissues were obtained from 13 patients with PC, 13 patients with parathyroid adenoma (PA) and 7 patients with parathyroid hyperplasia(PH), and 6 normal parathyroid (NP) tissues as controls. Peripheral blood from 11 patients with PC was collected. PCR products using Genomic DNA extracted from tumor tissues or blood as template was sequenced for HRPT2/CDC73 gene. Expression of parafibromin in tumor tissues was evaluated by immunohistochemical analysis.
  
  
  RESULTS
  Six mutations in 6 of 13 patients with PC were identified, with three being novel. Four of them were germ-line mutations. Patients with mutations were susceptible to recurrence of the PC. Complete (8/13, 61.5%) or partial (5/13, 38.5%) loss of parafibromin expression was observed in PC tissues. All of tissue samples from normal parathyroid or benign parathyroid tumors displayed positive immunostaining of parafibromin except one adenoma.
  
  
  CONCLUSIONS
  The present study supplies information on the mutations and protein expression of HRPT2/CDC73 gene and phenotypes of parathyroid carcinoma in Chinese population. And the expanded mutation database of this gene may benefit patients in the diagnosis and treatment of this disease.
authors.affiliation: Key laboratory of Endocrinology, Ministry of Health; Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
authors.forename: Ou
authors.initials: O
authors.lastname: Wang
authors.forename: Chunyan
authors.initials: C
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Nie
authors.forename: Quancai
authors.initials: Q
authors.lastname: Cui
authors.forename: Heng
authors.initials: H
authors.lastname: Guan
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.forename: Weibo
authors.initials: W
authors.lastname: Xia
authors.forename: Xunwu
authors.initials: X
authors.lastname: Meng
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Xing
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002681:China; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010282:Parathyroid Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: C454900:CDC73 protein, human; D025521:Tumor Suppressor Proteins