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Case report: a p.C618S RET proto-oncogene germline mutation in a large Chinese pedigree with familial medullary thyroid carcinoma

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Abstract

We report a Chinese pedigree with familial medullary thyroid carcinoma. Direct sequencing of the entire coding sequences of Rearranged during Transfection (RET) identified a recurrent c.T1852A (p.C618S) mutation in 13 of 23 members. The polymorphisms c.A135G (p.A45A), c.A1296G (p.A432A), c.T2307G (p.L769L) and IVS19 + 15T > C were also found in 13 carriers, and c.G2073A (p.G691S) was found in 1 carrier. Of the 13 carriers, seven (mean age: 42.6 years, range: 27–64) presented MTC as the isolated clinical phenotype, with elevated basal serum calcitonin (average: 1077.9 ng/L, range: 504–2,652) and a mean diameter of thyroid nodules of 2.97 cm (range: 1.6–4.3); they underwent a total thyroidectomy with modified bilateral/unilateral neck dissection and/or level VI lymph node dissection. The other 6 carriers did not accept surgery (4 rejected, 2 awaited). These were 2 older patients (63 and 32 years) with elevated calcitonin (1359 and 41.4 ng/L) and multi-centric hypoechoic nodules (1.5 and 0.6 cm) with calcifications in both/left thyroid lobes; and Doppler ultrasound showed normal bilateral thyroids in 4 younger carriers (median age: 8.3 years, range: 4–12) but with increased calcitonin (average: 9.7 ng/L, range: 7.87–12.2) in 3 of them. The phenotype here is consistent with the clinical symptoms reported worldwide. We recommend that screening of hotspot regions of RET should be preferentially carried out, while whole-exon sequencing should be performed when clinical signs fail to reveal hotspot mutations or different phenotype discrepancies. Moreover, we strongly suggest prophylactic thyroidectomy should be performed before age 5 in carriers with p.C618S to prevent the occurrence and metastasis of MTC.

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Abbreviations

ATA:

American Thyroid Association

CEA:

Carcinoembryonic antigen

Ct:

Calcitonin

CT:

Computerized tomography

FACLIA:

Fully-automated chemiluminescence immunoassay

FMTC:

Familial medullary thyroid carcinoma

HPT:

Hyperparathyroidism

HSCR:

Hirschsprung disease

MEN 2:

Multiple endocrine neoplasia type 2

MTC:

Medullary thyroid carcinoma

PHEO:

Pheochromocytoma

PTC:

Papillary thyroid carcinoma

RET :

REarranged during Transfection

SNPs:

Single nucleotide polymorphisms

US:

Ultrasound

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Acknowledgments

We thank all the patients and their families who agreed to participate in this study. This work was supported by the Key Scientific Research Project of Nanjing Military Command, China (09Z038 and 10Z036).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Departments of Urologic and Oncologic Surgery and Department of Pathology, The 117th PLA Hospital, 40 Jichang Road, Hangzhou, 310004, Zhejiang, China

    X.-P. Qi, J.-M. Ma, J. Fei, C.-P. Yang, Q.-Z. Song, H.-Y. Jin, Z.-G. Chen, J.-S. Han & J.-Q. Wang

  2. Department of Oncologic Surgery, Tumor Hospital of Taizhou, Wenling, Zhejiang, China

    R.-B. Ying

  3. Department of Biochemistry and Genetics, National Education Base for Basic Medical Sciences, Institute of Cell Biology, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou, 310058, Zhejiang, China

    W.-T. Liu, Z.-F. Du, X.-L. Chen, Y. Zhao, J.-J. Lu & X.-N. Zhang

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  1. X.-P. Qi
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  2. R.-B. Ying
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  3. J.-M. Ma
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  4. W.-T. Liu
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  9. H.-Y. Jin
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  11. J.-S. Han
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  12. J.-Q. Wang
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  13. X.-L. Chen
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  14. Y. Zhao
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  15. J.-J. Lu
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  16. X.-N. Zhang
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Corresponding authors

Correspondence to X.-P. Qi or X.-N. Zhang.

Additional information

X.-P. Qi, R.-B. Ying and X.-N. Zhang contributed equally to this work.

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Qi, XP., Ying, RB., Ma, JM. et al. Case report: a p.C618S RET proto-oncogene germline mutation in a large Chinese pedigree with familial medullary thyroid carcinoma. Familial Cancer 11, 131–136 (2012). https://doi.org/10.1007/s10689-011-9487-1

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  • DOI: https://doi.org/10.1007/s10689-011-9487-1

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