Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
September-2017 Volume 14 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
September-2017 Volume 14 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

A large Chinese pedigree of multiple endocrine neoplasia type 2A with a novel C634Y/D707E germline mutation in RET exon 11

  • Authors:
    • Fanqian Lu
    • Xiaohong Chen
    • Yunlong Bai
    • Yaru Feng
    • Jian Wu
  • View Affiliations / Copyright

    Affiliations: Department of Otolaryngology, Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, P.R. China, MyGenostics, Inc., Beijing 101318, P.R. China
    Copyright: © Lu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3552-3558
    |
    Published online on: July 15, 2017
       https://doi.org/10.3892/ol.2017.6583
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The present study identified the clinical features of the largest multiple endocrine neoplasia type 2 (MEN2) A pedigree from China, with a novel double missense rearranged during transfection (RET) mutation (C634Y/D707E). To the best of our knowledge, the D707E mutation has not been identified to date. In the present study, a total of 101 family members who originated from a large pedigree (134 members in total) underwent RET mutation screening by next‑generation sequencing and polymerase chain reaction (PCR) amplification, followed by direct bidirectional DNA sequencing. The clinical features of this pedigree were carefully reviewed retrospectively, and statistical analyses were conducted using SPSS software. A total of 33 (32.67%) carriers were identified to exhibit the C634Y/D707E RET germline mutation. The mean age of the patients with medullary thyroid carcinoma (MTC) identified by RET screening was 38.4±16.5 years (n=11; range, 14‑65 years). Only 4 patients with pheochromocytoma with a median age of 37 years were identified. No hyperparathyroidism was diagnosed. Persistent or recurrent disease developed in the patients of the present study who underwent inappropriate initial thyroid surgeries that were performed in previous decades (III10, III23, III24, III27 and IV46, as they had undergone two surgeries prior to the present study). A total of 66.70% (6/9) of patients, following thyroidectomy, continued to develop persistent or recurrent disease during the present screening study. In total, 3 patients succumbed to MTC or distant metastasis in the present study. The increase in carcinoembryonic antigen (CEA) levels correlated with the increase in basal serum calcitonin (Ct) levels according to Pearson correlation analysis in patients with MTC without surgery. Ct and CEA levels were also significantly correlated with tumor volumes. To the best of our knowledge, the present study is the first to identify a novel double RET missense mutation in the largest MEN2A pedigree from China. Additional in‑depth study is necessary to elucidate the molecular mechanisms of the D707E mutation and its potential joint effects with the other C634Y mutation in the pedigree of the present study.
View Figures

Figure 1

Figure 2

View References

1 

Machens A, Brauckhoff M, Holzhausen HJ, Thanh PN, Lehnert H and Dralle H: Codon-specific development of pheochromocytoma in multiple endocrine neoplasia type 2. J Clin Endocrinol Metab. 90:3999–4003. 2005. View Article : Google Scholar : PubMed/NCBI

2 

Wells SA Jr, Pacini F, Robinson BG and Santoro M: Multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma: An update. J Clin Endocrinol Metab. 98:3149–3164. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Kouvaraki MA, Shapiro SE, Perrier ND, Cote GJ, Gagel RF, Hoff AO, Sherman SI, Lee JE and Evans DB: RET proto-oncogene: A review and update of genotype-phenotype correlations in hereditary medullary thyroid cancer and associated endocrine tumors. Thyroid. 15:531–544. 2005. View Article : Google Scholar : PubMed/NCBI

4 

Brandi ML, Gagel RF, Angeli A, Bilezikian JP, Beck-Peccoz P, Bordi C, Conte-Devolx B, Falchetti A, Gheri RG, Libroia A, et al: Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab. 86:5658–5671. 2001. View Article : Google Scholar : PubMed/NCBI

5 

Trimboli P, Giovanella L, Crescenzi A, Romanelli F, Valabrega S, Spriano G, Cremonini N, Guglielmi R and Papini E: Medullary thyroid cancer diagnosis: An appraisal. Head Neck. 36:1216–1223. 2014. View Article : Google Scholar : PubMed/NCBI

6 

American Thyroid Association Guidelines Task Force, . Kloos RT, Eng C, Evans DB, Francis GL, Gagel RF, Gharib H, Moley JF, Pacini F, Ringel MD, et al: Medullary thyroid cancer: Management guidelines of the American Thyroid Association. Thyroid. 19:565–612. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Hu MI, Ying AK and Jimenez C: Update on medullary thyroid cancer. Endocrinol Metab Clin North Am. 43:423–442. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Toledo RA, Wagner SM, Coutinho FL, Lourenco DM Jr, Azevedo JA, Longuini VC, Reis MT, Siqueira SA, Lucon AM, Tavares MR, et al: High penetrance of pheochromocytoma associated with the novel C634Y/Y791F double germline mutation in the RET protooncogene. J Clin Endocrinol Metab. 95:1318–1327. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Cranston AN, Carniti C, Oakhill K, Radzio-Andzelm E, Stone EA, McCallion AS, Hodgson S, Clarke S, Mondellini P, Leyland J, et al: RET is constitutively activated by novel tandem mutations that alter the active site resulting in multiple endocrine neoplasia type 2B. Cancer Res. 66:10179–10187. 2006. View Article : Google Scholar : PubMed/NCBI

10 

Iwashita T, Murakami H, Kurokawa K, Kawai K, Miyauchi A, Futami H, Qiao S, Ichihara M and Takahashi M: A two-hit model for development of multiple endocrine neoplasia type 2B by RET mutations. Biochem Biophys Res Commun. 268:804–808. 2000. View Article : Google Scholar : PubMed/NCBI

11 

Barbieri RB, Bufalo NE, Secolin R, Silva AC, Assumpção LV, Maciel RM, Cerutti JM and Ward LS: Evidence that polymorphisms in detoxification genes modulate the susceptibility for sporadic medullary thyroid carcinoma. Eur J Endocrinol. 166:241–245. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Imai T, Uchino S, Okamoto T, Suzuki S, Kosugi S, Kikumori T and Sakurai A: MEN Consortium of Japan: High penetrance of pheochromocytoma in multiple endocrine neoplasia 2 caused by germ line RET codon 634 mutation in Japanese patients. Eur J Endocrinol. 168:683–687. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Sippel RS, Kunnimalaiyaan M and Chen H: Current management of medullary thyroid cancer. Oncologist. 13:539–547. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Dionigi G, Bianchi V, Rovera F, Boni L, Piantanida E, Tanda ML, Dionigi R and Bartalena L: Medullary thyroid carcinoma: Surgical treatment advances. Expert Rev Anticancer Ther. 7:877–885. 2007. View Article : Google Scholar : PubMed/NCBI

15 

Enewold L, Zhu K, Ron E, Marrogi AJ, Stojadinovic A, Peoples GE and Devesa SS: Rising thyroid cancer incidence in the United States by demographic and tumor characteristics, 1980–2005. Cancer Epidemiol Biomarkers Prev. 18:784–791. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Kebebew E, Ituarte PH, Siperstein AE, Duh QY and Clark OH: Medullary thyroid carcinoma: Clinical characteristics, treatment, prognostic factors, and a comparison of staging systems. Cancer. 88:1139–1148. 2000. View Article : Google Scholar : PubMed/NCBI

17 

Machens A, Ukkat J, Hauptmann S and Dralle H: Abnormal carcinoembryonic antigen levels and medullary thyroid cancer progression: A multivariate analysis. Arch Surg. 142:289–294. 2007. View Article : Google Scholar : PubMed/NCBI

18 

Chen Z, Qi X, Fei J, Yu X, Zhao Y, Zhao J, Jin H, Wang J, Ying R and Zhang X: Multiple endocrine neoplasia type 2A caused by a p.C618R RET proto-oncogene mutation in a Chinese pedigree. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 31:348–351. 2014.(In Chinese). PubMed/NCBI

19 

Schreinemakers JM, Vriens MR, Valk GD, de Groot JW, Plukker JT, Bax K, Hamming JF, van der Luijt RB, Aronson DC and Borel Rinkes IH: Factors predicting outcome of total thyroidectomy in young patients with multiple endocrine neoplasia type 2: A nationwide long-term follow-up study. World J Surg. 34:852–860. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Niederle B, Sebag F and Brauckhoff M: Timing and extent of thyroid surgery for gene carriers of hereditary C cell disease-a consensus statement of the European society of endocrine surgeons (ESES). Langenbecks Arch Surg. 399:185–197. 2014. View Article : Google Scholar : PubMed/NCBI

21 

Machens A, Ukkat J, Brauckhoff M, Gimm O and Dralle H: Advances in the management of hereditary medullary thyroid cancer. J Intern Med. 257:50–59. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Kaserer K, Scheuba C, Neuhold N, Weinhäusel A, Vierhapper H and Niederle B: Recommendations for reporting C cell pathology of the thyroid. Wien Klin Wochenschr. 114:274–278. 2002.PubMed/NCBI

23 

Kaserer K, Scheuba C, Neuhold N, Weinhäusel A, Haas OA, Vierhapper H and Niederle B: Sporadic versus familial medullary thyroid microcarcinoma: A histopathologic study of 50 consecutive patients. Am J Surg Pathol. 25:1245–1251. 2001. View Article : Google Scholar : PubMed/NCBI

24 

Wolfe HJ, Melvin KE, Cervi-Skinner SJ, Saadi AA, Juliar JF, Jackson CE and Tashjian AH Jr: C-cell hyperplasia preceding medullary thyroid carcinoma. N Engl J Med. 289:437–441. 1973. View Article : Google Scholar : PubMed/NCBI

25 

Kurzrock R, Atkins J, Wheler J, Fu S, Naing A, Busaidy N, Hong D and Sherman S: Tumor marker and measurement fluctuations may not reflect treatment efficacy in patients with medullary thyroid carcinoma on long-term RET inhibitor therapy. Ann Oncol. 24:2256–2261. 2013. View Article : Google Scholar : PubMed/NCBI

26 

Shively JE and Beatty JD: CEA-related antigens: Molecular biology and clinical significance. Crit Rev Oncol Hematol. 2:355–399. 1985. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Lu F, Chen X, Bai Y, Feng Y and Wu J: A large Chinese pedigree of multiple endocrine neoplasia type 2A with a novel C634Y/D707E germline mutation in RET exon 11. Oncol Lett 14: 3552-3558, 2017.
APA
Lu, F., Chen, X., Bai, Y., Feng, Y., & Wu, J. (2017). A large Chinese pedigree of multiple endocrine neoplasia type 2A with a novel C634Y/D707E germline mutation in RET exon 11. Oncology Letters, 14, 3552-3558. https://doi.org/10.3892/ol.2017.6583
MLA
Lu, F., Chen, X., Bai, Y., Feng, Y., Wu, J."A large Chinese pedigree of multiple endocrine neoplasia type 2A with a novel C634Y/D707E germline mutation in RET exon 11". Oncology Letters 14.3 (2017): 3552-3558.
Chicago
Lu, F., Chen, X., Bai, Y., Feng, Y., Wu, J."A large Chinese pedigree of multiple endocrine neoplasia type 2A with a novel C634Y/D707E germline mutation in RET exon 11". Oncology Letters 14, no. 3 (2017): 3552-3558. https://doi.org/10.3892/ol.2017.6583
Copy and paste a formatted citation
x
Spandidos Publications style
Lu F, Chen X, Bai Y, Feng Y and Wu J: A large Chinese pedigree of multiple endocrine neoplasia type 2A with a novel C634Y/D707E germline mutation in RET exon 11. Oncol Lett 14: 3552-3558, 2017.
APA
Lu, F., Chen, X., Bai, Y., Feng, Y., & Wu, J. (2017). A large Chinese pedigree of multiple endocrine neoplasia type 2A with a novel C634Y/D707E germline mutation in RET exon 11. Oncology Letters, 14, 3552-3558. https://doi.org/10.3892/ol.2017.6583
MLA
Lu, F., Chen, X., Bai, Y., Feng, Y., Wu, J."A large Chinese pedigree of multiple endocrine neoplasia type 2A with a novel C634Y/D707E germline mutation in RET exon 11". Oncology Letters 14.3 (2017): 3552-3558.
Chicago
Lu, F., Chen, X., Bai, Y., Feng, Y., Wu, J."A large Chinese pedigree of multiple endocrine neoplasia type 2A with a novel C634Y/D707E germline mutation in RET exon 11". Oncology Letters 14, no. 3 (2017): 3552-3558. https://doi.org/10.3892/ol.2017.6583
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team