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.

Distribution ofRETMutations in Multiple Endocrine Neoplasia 2 in Denmark 1994–2014: A Nationwide Study

“…Codon 634 mutations have been reported as the most predominant in several European ( Table 3 ) ( 6–14 ) and non-European series ( Table 4 ) ( 17–25 ). This might be explained by earlier onset of disease and a presentation frequently involving the full-blown MEN2 syndrome (MTC, PHEO, and HPTH).…”

“…Codon 634 mutations are reported as the most prevalent in both European ( 6–16 ) and non-European families ( 17–25 ). However, a recent Greek study of 58 RET positive families found mutations of codon 533 to be predominant ( 26 ).…”

Genetic and Clinical Features of Medullary Thyroid Carcinoma: The Experience of a Single Center in Costa Rica

“…Similarly, the majority of MEN 2B patients presented clinical manifestations in the second decade of life and needed to have a total thyroidectomy when they were initially diagnosed [8]. Particularly in this patient, the same mutation was not detected in his mother nor had a history of medullary carcinoma been detected in his paternal or maternal relatives, suggesting that this mutation occurred de novo , which is a relatively common finding, as approximately 75% of MEN 2B patients have de novo RET mutations [22]. …”

The use of nutraceuticals in male sexual and reproductive disturbances: position statement from the Italian Society of Andrology and Sexual Medicine (SIAMS)

“…In 85% of MEN2A patients, RET codon 634 (p.Cys634Arg) has been reported as the most prevalent in European and non-European families [18,20,26]. Several other smaller and larger multicenter studies mainly from groups around Europe demonstrated codon 533 as the prevailing in Greece [27], 611 in Portugal and Denmark [28,29], 618 in Cyprus [15], 790 in Germany [18] and 804 and 891 in Italy [19].…”