Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2016 Mar 5;8(1):13-20.
doi: 10.4274/jcrpe.2219. Epub 2015 Dec 18.

Distribution of RET Mutations and Evaluation of Treatment Approaches in Hereditary Medullary Thyroid Carcinoma in Turkey

Berna İmge Aydoğan  1 , Bağdagül Yüksel, Mazhar Müslüm Tuna, Mehtap Navdar Başaran, Ayşen Akkurt Kocaeli, Melek Eda Ertörer, Kadriye Aydın, Sibel Güldiken, Yasin Şimşek, Züleyha Cihan Karaca, Merve Yılmaz, Müjde Aktürk, İnan Anaforoğlu, Nur Kebapçı, Cevdet Duran, Abdullah Taşlıpınar, Mustafa Kulaksızoğlu, Alptekin Gürsoy, Selçuk Dağdelen, Murat Faik Erdoğan
Affiliations
Multicenter Study

Distribution of RET Mutations and Evaluation of Treatment Approaches in Hereditary Medullary Thyroid Carcinoma in Turkey

Berna İmge Aydoğan et al. J Clin Res Pediatr Endocrinol. .

Abstract

Objective: This retrospective multicenter study, centrally conducted and supported by the Society of Endocrinology and Metabolism of Turkey, aimed to evaluate the impact of free RET proto-oncogene testing in medullary thyroid carcinoma (MTC) patients. Surgical timing, adequacy of the treatment, and frequency of prophylactic thyroidectomy (PTx) in mutation carriers were also assessed.

Methods: Genetic testing for MTC and pheochromocytoma was conducted between July 2008 and January 2012 in 512 patients. Application forms and RET mutation analyses of these patients whose blood samples were sent from various centers around Turkey were assessed retrospectively. An evaluation form was sent to the physicians of the eligible 319 patients who had confirmed sporadic MTC, familial MTC (FMTC), multiple endocrine neoplasia type 2 (MEN2), or who were mutation carriers. Physicians were asked to give information about the surgical history, latest calcitonin levels, morbidity, mortality, genetic screening, and PTx among family members. Twenty-five centers responded by filling in the forms of 192 patients.

Results: Among the 319 patients, RET mutation was detected in 71 (22.3%). Cys634Arg mutation was the most prevalent mutation (43.7%), followed by Val804Met in 18 patients (25.4%), and Cys634Tyr in 6 patients (8.5%). Among 192 MTC patients, the diagnosis was sporadic MTC in 146 (76.4%), FMTC in 14 (7.3%), MEN2A in 15 patients (7.9%), and MEN2B in one patient. The number of mutation carriers among 154 apparently sporadic MTC patients was 8 (5.2%). Ten patients were submitted to PTx out of twenty-four mutation carriers at a mean age of 35±19 years.

Conclusion: Turkish people have a similar RET proto-oncogene mutation distribution when compared to other Mediterranean countries. Despite free RET gene testing, the number of the PTx in Turkey is limited and relatively late in the life span of the carriers. This is mainly due to patient and family incompliance and incomplete family counselling.

PubMed Disclaimer

Figures

Figure 1
Figure 1. The distrubition of diagnosis for 191 medullary thyroid carcinoma patients with available clinical information (multiple endocrine neoplasia type 2 B patient was excluded). MTC: Medullary thyroid carcinoma, MEN2A: multiple endocrine neoplasia type 2 A
See this image and copyright information in PMC

References

    1. Marsh DJ, Learoyd DL, Robinson BG. Medullary thyroid carcinoma: recent advances and management update. Thyroid. 1995;5:407–424. - PubMed
    1. Machens A, Lorenz K, Dralle H. Constitutive RET tyrosine kinase activation in hereditary medullary thyroid cancer: clinical opportunities. J Intern Med. 2009;266:114–125. - PubMed
    1. Eng C, Clayton D, Schuffenecker I, Lenoir G, Cote G, Gagel RF, Amstel HK, van, Lips CJ, Nishisho I, Takai SI, Marsh DJ, Robinson BG, Frank-Raue K, Raue F, Xue F, Noll WW, Romei C, Pacini F, Fink M, Niederle B, Zedenius J, Nordenskjöld M, Komminoth P, Hendy GN, Mulligan LM, et al. The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis. JAMA. 1996;276:1575–1579. - PubMed
    1. Raue F, Frank-Raue K, Grauer A. Multiple endocrine neoplasia type 2. Clinical features and screening. Endocrinol Metab Clin North Am. 1994;23:137–156. - PubMed
    1. Gagel RF, Levy ML, Donovan DT, Alford BR, Wheeler T, Tschen JA. Multiple endocrine neoplasia type 2a associated with cutaneous lichen amyloidosis. Ann Intern Med. 1989;111:802–806. - PubMed

Publication types

MeSH terms

Supplementary concepts

LinkOut - more resources