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Screening of RET gene mutations in Chinese patients with medullary thyroid carcinoma and their relatives

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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.

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Acknowledgments

This research was supported by Grants from Research Fund for the Doctoral Program of Higher Education of China (20101106110016) and Graduate Innovation Foundation of Peking Union Medical College (20101002016).

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Authors and Affiliations

  1. 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

    Junyi Wang

  2. Department of Head and Neck Surgery, Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100021, China

    Bin Zhang, Wensheng Liu, Yanmei Yang & Dangui Yan

  3. Department of Otorhinolaryngology, Head and Neck Surgery, Tianjin Medical University General Hospital, Tianjin, 300052, China

    Yongxia Zhang

  4. Department of Etiology and Carcinogenesis, Cancer Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100021, China

    Xuebing Di

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  1. Junyi Wang
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  2. Bin Zhang
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  3. Wensheng Liu
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  4. Yongxia Zhang
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  5. Xuebing Di
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  6. Yanmei Yang
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  7. Dangui Yan
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Correspondence to Bin Zhang.

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The authors declare that there is no conflict of interest in this work.

Ethical approval

Ethical approval was given by the Human Research Ethics Committee of the Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, with the following Approval Number: 11-05/440.

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Informed consent was obtained from all individual participants included in the study.

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Wang, J., Zhang, B., Liu, W. et al. Screening of RET gene mutations in Chinese patients with medullary thyroid carcinoma and their relatives. Familial Cancer 15, 99–104 (2016). https://doi.org/10.1007/s10689-015-9828-6

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