title: Screening of RET gene mutations in Chinese patients with medullary thyroid carcinoma and their relatives.
abstract: The rearranged during transfection (RET) gene is a proto-oncogene; active mutations frequently occur in medullary thyroid carcinoma (MTC). This study investigated the spectrum of germline RET mutations and clinical features in Chinese hereditary MTC patients. A total of 53 family members from 11 different hereditary MTC families were recruited for detection of RET exon 8, 10, 11, 13, 14, 15, and 16 mutations, in genomic DNA from peripheral blood leucocytes using polymerase chain reaction (PCR) and direct DNA sequencing. Of the 53 participants, eight different germline RET mutations were detected in 37 individuals. These RET mutations were distributed in exons 10, 11, 13, and 16. The most frequent RET mutation was localized at exon 11 codon 634 (67.6 %; 25/37) and the most prevalent mutation was C634R (37.8 %; 14/37). The most frequent phenotype was multiple endocrine neoplasia type 2A (MEN2A). The incidences of MTC, pheochromocytoma, and hyperparathyroidism in the MEN2A patients were 100, 36.4 and 18.2 %, respectively. The phenotype of families with Y606C or L790F mutation was categorized as familial medullary thyroid carcinoma. Moreover, one proband was identified with multiple endocrine neoplasia type 2B and carried a de novo mutation of M918T. Two families with C618S/Y mutation were categorized as unclassified multiple endocrine neoplasia type 2. Our results further substantiate that most germline mutations of the RET proto-oncogene were localized at codon 634 in Chinese hereditary MTC patients and carriers. RET mutation at codon 634 was always associated to the phenotype of MEN2A. Screening of RET mutations should be probably limited to exons 10, 11, 13 and 16 initially to be cost-effective in China.
authors.affiliation: Key Laboratory of Cancer Prevention and Therapy of Tianjin, Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, 300060, China.
authors.forename: Junyi
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Head and Neck Surgery, Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100021, China. jzxsya@126.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Head and Neck Surgery, Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100021, China.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Tianjin Medical University General Hospital, Tianjin, 300052, China.
authors.forename: Yongxia
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Etiology and Carcinogenesis, Cancer Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100021, China.
authors.forename: Xuebing
authors.initials: X
authors.lastname: Di
authors.affiliation: Department of Head and Neck Surgery, Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100021, China.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Head and Neck Surgery, Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100021, China.
authors.forename: Dangui
authors.initials: D
authors.lastname: Yan
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D018276:Carcinoma, Medullary / Q000151:congenital* / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics*; D055815:Young Adult
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human
keywords: Cancer; Germline mutation; Medullary thyroid carcinoma; RET proto-oncogene; Thyroid