title: RET proto-oncogene mutations are restricted to codons 634 and 918 in mainland Chinese families with MEN2A and MEN2B.
abstract: OBJECTIVE
  Multiple endocrine neoplasia type 2 is caused by autosomal dominant gain-of-function mutations in the RET proto-oncogene, which includes multiple endocrine neoplasia type 2A (MEN2A), type 2B (MEN 2B), and familial medullary thyroid carcinoma (FMTC). In this paper we present the phenotype-genotype correlation of 20 unrelated Chinese families with 15 cases of MEN2A and five cases of MEN2B.
  
  
  METHODS
  Cross-sectional study.
  
  
  METHODS
  A total of 147 members from the 20 families were included. Among them, 119 family members were from MEN2A pedigrees (including 15 MEN2A probands) and 28 members from MEN2B pedigrees (including five MEN2B probands).
  
  
  METHODS
  Genomic DNA was isolated from peripheral blood leucocytes and was amplified using polymerase chain reaction (PCR). DNA analysis for RET mutations in exons 8, 10, 11, 13, 14, 15 and 16 was performed with specific primers.
  
  
  RESULTS
  Thirty-seven MEN2A and five MEN2B patients were identified as having RET mutations. The incidence of medullary thyroid carcinoma (MTC), pheochromocytoma (PCC) and hyperparathyroidism (HPT) in the 37 MEN2A patients was 91.9, 56.8 and 10.8%, respectively; the onset of MTC in MEN2A patients was earlier than that of PCC and HPT. Five germline mutations, all located at codon 634 of exon11 in the RET proto-oncogene, were detected in all of the 37 MEN2A patients. The highest frequency of the five germline mutations was C634Y (46.7%), followed by C634R (26.7%), C634W (13.3%), C634F (6.7%) and C634S (6.7%). No statistical significance was found between the incidence of PCC and different genotypes of codon 634 in MEN2A patients, whereas the incidence of HPT was closely associated with C634R and C634Y. The gene mutation (M918T) at exon16 of the RET proto-oncogene was present in five MEN2B probands.
  
  
  CONCLUSIONS
  RET proto-oncogene mutations were restricted to codon 634 and 918 in Chinese families with MEN2A and MEN2B. In general the genetic characteristics of these patients with MEN2A and MEN2B reflect the general pattern around the world and it remains to be determined with larger studies in China whether Chinese patients have a different genetic pattern of mutations.
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Key Laboratory for Endocrine Tumors, Ruijin Hospital, Jiao Tong University, Shanghai.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Zhou
authors.forename: Yongju
authors.initials: Y
authors.lastname: Zhao
authors.forename: Bin
authors.initials: B
authors.lastname: Cui
authors.forename: Liqun
authors.initials: L
authors.lastname: Gu
authors.forename: Shaoxin
authors.initials: S
authors.lastname: Zhu
authors.forename: Jianjun
authors.initials: J
authors.lastname: Li
authors.forename: Jinbo
authors.initials: J
authors.lastname: Liu
authors.forename: Ming
authors.initials: M
authors.lastname: Yin
authors.forename: Tieyun
authors.initials: T
authors.lastname: Zhao
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Yin
authors.forename: Chaoli
authors.initials: C
authors.lastname: Yu
authors.forename: Changyou
authors.initials: C
authors.lastname: Chen
authors.forename: Liming
authors.initials: L
authors.lastname: Wang
authors.forename: Buyun
authors.initials: B
authors.lastname: Xiao
authors.forename: Jie
authors.initials: J
authors.lastname: Hong
authors.forename: Yifei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhengyi
authors.initials: Z
authors.lastname: Tang
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Li
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
mesh_terms: D000328:Adult; D000368:Aged; D002681:China; D003062:Codon; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics*; D018814:Multiple Endocrine Neoplasia Type 2b / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*
chemical_list: D003062:Codon; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret