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Somatic mutation testing: the role in differential diagnosis of thyroid neoplasms


Background: In the preoperative diagnosis of thyroid tumors the cytological examination of the material of fine needle aspiration biopsy is the gold standard and serves as the basis for planning of treatment strategy. However, in 10-30% of cases, it cannot be clearly established by cytology whether the nature of thyroid neoplasm benign or malignant, which leads to the inability to choose the optimal treatment strategy in advance. For such cases, it is extremely important to search for methods of clarifying differential diagnosis, among which mutation testing is currently considered the most promising.
Aims: to evaluate the possibility of using mutation tests for clarifying differential diagnosis of thyroid neoplasms at the preoperative stage.
Materials and methods: a prospective, single centre study was performed, which included patients with the thyroid neoplasms, who had been treated in the Endocrinology Research Center, Moscow, Russia from 2012 to 2014. Samples of histological material, cytological material and blood plasma of these patients were tested for the presence of somatic mutations in hot spots of the genes BRAF, KRAS, NRAS, TERT, and EIF1AX.
Results: the study included 75 patients, 29 of them with low-risk well differentiated thyroid cancer, 29 with undetermined tumors of the thyroid gland and 17 with colloid nodular goiter. Mutations in the" hot spots "of the BRAF gene (exon 15, codon area 600-601) were found in 29 patients, mutations in the" hot spots " of the NRAS gene (exon 3, codon 61) – in 8 patients; mutations in the hot spots of the KRAS, TERT and EIF1AX genes were not detected. Correlation of the results of mutational testing of cytological and histological material was 91,7%. Mutations of tumor origin in circulating blood plasma DNA were found in only 1 cases. The prognostic value of the positive result (PPV) of the mutation test on cytological material in relation to the malignant nature of the thyroid tumor was 100% for the BRAF gene and 0% for the NRAS gene.
Conclusions: the mutation test in the "hot spots" of the BRAF gene on cytological material can be used as an additional marker to clarify the nature of thyroid tumors, when the result of cytological examination are uncertain. Either in similar situations for mutation tests in the" hot spots " of genes KRAS, NRAS, EIF1AX and TERT on cytological material, or mutation testing of circulating DNA of blood plasma can’t be used as an additional marker.

Vera Kachko

I.M. Sechenov First Moscow State Medical University (Sechenov University), Department of Endocrinology, Moscow, Russia

Author for correspondence.
Email: VeraF246@gmail.com
ORCID iD: 0000-0002-0617-7312
SPIN-code: 5869-7470

Russian Federation, 8-2 Trubetskaya str.  Moscow, Russian Federation 119991 


Andrew Zaretsky

Evrogen Lab LLC, Moscow, Russia || Shemyakin-Ovchinnikov Research Institute for Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia

Email: a-zaretsky@yandex.ru

Russian Federation, Russia , 117997, Moscow , Miklukho-Maklaya, 16/10

the head of the Department of molecular Oncology

Vladimir Vanushko

Endocrinology Research Centre, Moscow, Russia

Email: vanushko@gmail.com
ORCID iD: 0000-0001-6338-7490
SPIN-code: 6097-8990

Russian Federation, 11 Dm.Ulyanova street, 117036 Moscow, Russia

MD, PhD, chief researcher of the Department of surgery

Nadezhda Platonova

Endocrinology Research Centre, Moscow, Russia

Email: doc-platonova@inbox.ru
ORCID iD: 0000-0001-6388-1544
SPIN-code: 4053-3033

Russian Federation, 11 Dm.Ulyanova street, 117036 Moscow, Russia

MD, PhD, chief researcher of the Department of therapeutic endocrinology

Aleksandr Abrosimov

Endocrinology Research Centre, Moscow, Russia

Email: nikitarusskikh@mail.ru
ORCID iD: 0000-0001-8284-9996
SPIN-code: 4089-9502

Russian Federation, 11 Dm.Ulyanova street, 117036 Moscow, Russia

MD, PhD, head of the Department of fundamental pathomorphology

Galina Semkina

Endocrinology Research Centre, Moscow, Russia

Email: stefana86@mail.ru
ORCID iD: 0000-0002-2135-4372
SPIN-code: 3483-5837

Russian Federation, 11 Dm.Ulyanova street, 117036 Moscow, Russia


  • Ali SZ, Cibas ES. The 2017 Bethesda System for Reporting Thyroid Cytopathology. J Am Soc Cytopathol. 2017; 6:217-222. doi: 10.1016/j.jasc.2017.09.002.
  • Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016; 26:1-133. doi: 10.1089/thy.2015.0020.
  • Hsiao SJ., Nikiforov YE. Molecular Approaches to Thyroid Cancer Diagnosis Endocr Relat Cancer. 2014;21(5) :T301–T313. doi: 10.1530/ERC-14-0166.
  • Wei X, Li Y, Zhang S, Gao M, Meta-analysis of thyroid imaging reporting and data system in the ultrasonographic diagnosis of 10,437 thyroid nodules. Head Neck. 2016;38(2):309-15. doi: 10.1002/hed.23878.
  • Бельцевич Д.Г., Ванушко В.Э., Румянцев П.О. и др. Российские клинические рекомендации по диагностике и лечению высокодифференцированного рака щитовидной железы у взрослых, 2017 год. // Эндокринная хирургия. – 2017. – Т. 11. – №1. – С. 6–27. doi: 10.14341/serg201716-27. [Beltsevich DG, Vanushko VE, Rumyantsev PO, et al. 2017 Russian clinical practice guidelines for differentiated thyroid cancer diagnosis and treatment. Endocrine Surgery. 2017;11(1):6 -27. doi: 10.14341/serg201716. -27.(In Russ).]
  • Agrawal N, Jiao Y, Sausen M, et al. Exomic sequencing of medullary thyroid cancer reveals dominant and mutually exclusive oncogenic mutations in RET and RAS. J Clin Endocrinol Metab. 2013;98:E364–369. doi: 10.1210/jc.2012-2703.
  • Rossi M, Buratto M, Tagliati F et al. Relevance of BRAF(V600E) mutation testing versus RAS point mutations and RET/PTC rearrangements evaluation in the diagnosis of thyroid cancer. Thyroid. 2015;25(2): 221–228. doi: 10.1089/thy.2014.0338.
  • Seo JY, Kim EK, Kwak JY. Additional BRAF mutation analysis may have additional diagnostic value in thyroid nodules with “suspicious for malignant” cytology alone even when the nodules do not show suspicious US features. Endocrine. 2014;47(1): 283–289. doi: 10.1007/s12020-013-0150-5.
  • Koh J, Choi JR, Han KH et al. Proper indication of BRAF(V600E) mutation testing in fine-needle aspirates of thyroid nodules. PLoS One. 2013;8(5):e64505. doi: 10.1371/journal.pone.0064505.
  • Gandolfi G., Ragazzi M., Frasoldati A., Piana S., Ciarrocchi A., Sancisi V. TERT promoter mutations are associated with distant metastases in papillary thyroid carcinoma. Eur. J. Endocrinol. 2015; 172:403–413. doi: 10.1530/EJE-14-0837.
  • Liu X., Qu S., Liu R., Sheng C., Shi X., Zhu G., Murugan A.K., Guan H., Yu H., Wang Y., et al. TERT promoter mutations and their association with BRAF V600E mutation and aggressive clinicopathological characteristics of thyroid cancer. J. Clin. Endocrinol. Metab. 2014;99: E1130–E1136. doi: 10.1210/jc.2013-4048.
  • Liu, T., Yuan, X., & Xu, D. (2016). Cancer-Specific Telomerase Reverse Transcriptase (TERT) Promoter Mutations: Biological and Clinical Implications. Genes, 7(7), 38. doi: 10.3390/genes7070038.
  • Karunamurthy A, Panebianco F, J Hsiao S, et al. Prevalence and phenotypic correlations of EIF1AX mutations in thyroid nodules. Endocr Relat Cancer. 2016;23(4):295-301. doi: 10.1530/ERC-16-0043.
  • Molecular pathogenesis and mechanisms of thyroid cancer. Nat Rev Cancer. 2013; 13(3):184-99. doi: 10.1038/nrc3431.
  • Oncogenesis of Thyroid Cancer. Asian Pac J Cancer Prev. 2017;18(5):1191-1199. doi: 10.22034/APJCP.2017.18.5.1191.
  • COSMIC [Internet]. Catalogue Of Somatic Mutations In Cancer [cited 2018 Dec 12]. Available from: https://cancer.sanger.ac.uk/cosmic
  • EnsEMBL [Internet]. Genome browser [cited 2018 Dec 12]. Available from: http://www.ensembl.org


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Copyright (c) Kachko V., Zaretsky A., Vanushko V., Platonova N., Abrosimov A., Semkina G.

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