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Correlation between TERT C228T and clinic-pathological features in pediatric papillary thyroid carcinoma

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Abstract

The aims of the present study were to reveal the prevalence of the TERT C228T mutation in pediatric papillary thyroid carcinoma (PPTC) and to further investigate the role of the TERT C228T mutation in PPTC. We also tested another TERT mutation, TERT C250T, although this was not detected in PPTC patients. In this study, 48 patients with PPTC (41 with classic PPTC) were enrolled. DNA was extracted from PPTC tissues and TERT C228T mutation analysis was performed. Chi-squared analysis, Fisher’s exact test, and a t-test were applied to test the significance of differences. The TERT C228T mutation presented in 13 (27.1%) of the 48 PPTC patients and 10 (24.4%) of the 41 classical PPTC patients. There were significant differences between PPTC patients with the TERT C228T mutation and those without in terms of modified radical neck dissection, multifocality, capsular invasion, extrathyroidal invasion, and American Joint Committee on Cancer (AJCC) tumor stage (P<0.05). In classical PPTC, there were additional significant differences in other clinic-pathological features, such as AJCC nodal stage (P=0.009) and American Thyroid Association (ATA) PPTC stage (P=0.021) between patients with and without the TERT C228T mutation. These findings indicate that the TERT C228T mutation is significantly correlated with certain aggressive clinic-pathological features of PPTC.

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References

  • Adam, M.A., Pura, J., Gu, L., Dinan, M.A., Tyler, D.S., Reed, S.D., Scheri, R., Roman, S.A., and Sosa, J.A. (2014). Extent of surgery for papillary thyroid cancer is not associated with survival. Ann Surgery 260, 601–607.

    Google Scholar 

  • Alzahrani, A.S., Alsaadi, R., Murugan, A.K., and Sadiq, B.B. (2016a). TERT promoter mutations in thyroid cancer. Horm Cancer 7, 165–177.

    CAS  PubMed  Google Scholar 

  • Alzahrani, A.S., Qasem, E., Murugan, A.K., Al-Hindi, H.N., AlKhafaji, D., Almohanna, M., Xing, M., Alhomaidah, D., and AlSwailem, M. (2016b). Uncommon TERT promoter mutations in pediatric thyroid cancer. Thyroid 26, 235–241.

    CAS  PubMed  Google Scholar 

  • Bae, J.S., Kim, Y., Jeon, S., Kim, S.H., Kim, T.J., Lee, S., Kim, M.H., Lim, D.J., Lee, Y.S., and Jung, C.K. (2016). Clinical utility of TERT promoter mutations and ALK rearrangement in thyroid cancer patients with a high prevalence of the BRAF V600E mutation. Diagn Pathol 11, 21.

    PubMed  PubMed Central  Google Scholar 

  • Carcangiu, M.L., Zampi, G., Pupi, A., Castagnoli, A., and Rosai, J. (1985). Papillary carcinoma of the thyroid. A clinicopathologic study of 241 cases treated at the University of Florence, Italy. Cancer 55, 805–828.

    CAS  PubMed  Google Scholar 

  • Chung, Y.S., Kim, J.Y., Bae, J.S., Song, B.J., Kim, J.S., Jeon, H.M., Jeong, S.S., Kim, E.K., and Park, W.C. (2009). Lateral lymph node metastasis in papillary thyroid carcinoma: results of therapeutic lymph node dissection. Thyroid 19, 241–246.

    PubMed  Google Scholar 

  • Crescenzi, A., Trimboli, P., Modica, D.C., Taffon, C., Guidobaldi, L., Taccogna, S., Rainer, A., Trombetta, M., Papini, E., and Zelano, G. (2016). Preoperative assessment of TERT promoter mutation on thyroid core needle biopsies supports diagnosis of malignancy and addresses surgical strategy. Horm Metab Res 48, 157–162.

    CAS  PubMed  Google Scholar 

  • Dzodic, R., Buta, M., Markovic, I., Gavrilovic, D., Matovic, M., Djurisic, I., Milovanovic, Z., Pupic, G., Tasic, S., and Besic, N. (2014). Surgical management of well-differentiated thyroid carcinoma in children and adolescents: 33 years of experience of a single institution in Serbia. Endocr J 61, 1079–1086.

    PubMed  Google Scholar 

  • Francis, G.L., Waguespack, S.G., Bauer, A.J., Angelos, P., Benvenga, S., Cerutti, J.M., Dinauer, C.A., Hamilton, J., Hay, I.D., Luster, M., et al. (2015). Management guidelines for children with thyroid nodules and differentiated thyroid cancer. Thyroid 25, 716–759.

    PubMed  PubMed Central  Google Scholar 

  • Gandolfi, G., Ragazzi, M., Frasoldati, A., Piana, S., Ciarrocchi, A., and Sancisi, V. (2015). TERT promoter mutations are associated with distant metastases in papillary thyroid carcinoma. Eur J Endocrinol 172, 403–413.

    CAS  PubMed  Google Scholar 

  • Geng, J., Tai, J., Wei, B., Guo, Y., and Ni, X. (2014). The etiology, diagnosis and treatment of differentiated thyroid carcinoma in children and adolescents. Am J Biomed Sci Sci, 254–264.

    Google Scholar 

  • Geng, J., Wang, H., Liu, Y., Tai, J., Jin, Y., Zhang, J., He, L., Fu, L., Qin, H., Song, Y., et al. (2017). Correlation between BRAF V600E mutation and clinicopathological features in pediatric papillary thyroid carcinoma. Sci China Life Sci 60, 729–738.

    CAS  PubMed  Google Scholar 

  • Gertz, R.J., Nikiforov, Y., Rehrauer, W., McDaniel, L., and Lloyd, R.V. (2016). Mutation in BRAF and other members of the MAPK pathway in papillary thyroid carcinoma in the pediatric population. Arch Pathol Lab Med 140, 134–139.

    CAS  PubMed  Google Scholar 

  • Hao, C., Guo, J., Guo, R., Qi, Z., Li, W., and Ni, X. (2018). Compound heterozygous variants in POR gene identified by whole-exome sequencing in a Chinese pedigree with cytochrome P450 oxidoreductase deficiency. Pediatr Invest 2, 90–95.

    Google Scholar 

  • Hartl, D.M., Leboulleux, S., Al Ghuzlan, A., Baudin, E., Chami, L., Schlumberger, M., and Travagli, J.P. (2012). Optimization of staging of the neck with prophylactic central and lateral neck dissection for papillary thyroid carcinoma. Ann Surgery 255, 777–783.

    Google Scholar 

  • Hilger, R.A., Scheulen, M.E., and Strumberg, D. (2002). The Ras-Raf-MEK-ERK pathway in the treatment of cancer. Oncol Res Treat 25, 511–518.

    CAS  Google Scholar 

  • Hogan, A.R., Zhuge, Y., Perez, E.A., Koniaris, L.G., Lew, J.I., and Sola, J. E. (2009). Pediatric thyroid carcinoma: incidence and outcomes in 1753 patients. J Surg Res 156, 167–172.

    PubMed  Google Scholar 

  • Jeon, M.J., Kim, W.G., Sim, S., Lim, S., Kwon, H., Kim, T.Y., Shong, Y.K., and Kim, W.B. (2016). Low prevalence of somatic TERT promoter mutations in classic papillary thyroid carcinoma. Endocrinol Metab 31, 100–104.

    CAS  Google Scholar 

  • Jeon, M.J., Kim, W.G., Choi, Y.M., Kwon, H., Song, D.E., Lee, Y.M., Sung, T.Y., Yoon, J.H., Hong, S.J., Baek, J.H., et al. (2015a). Recent changes in the clinical outcome of papillary thyroid carcinoma with cervical lymph node metastasis. J Clin Endocrinol Metab 100, 3470–3477.

    CAS  PubMed  Google Scholar 

  • Jeon, M.J., Kim, W.G., Jang, E.K., Choi, Y.M., Song, D.E., Sung, T.Y., Yoon, J.H., Chung, K.W., Hong, S.J., Ryu, J.S., et al. (2015b). Sub-Classification of Lateral Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma by Pathologic Criteria. PLoS ONE 10, e0133625.

    PubMed  PubMed Central  Google Scholar 

  • Jin, L., Chen, E., Dong, S., Cai, Y., Zhang, X., Zhou, Y., Zeng, R., Yang, F., Pan, C., Liu, Y., et al. (2016). BRAF and TERT promoter mutations in the aggressiveness of papillary thyroid carcinoma: a study of 653 patients. Oncotarget 7.

    Google Scholar 

  • Killela, P.J., Reitman, Z.J., Jiao, Y., Bettegowda, C., Agrawal, N., Diaz Jr., L.A., Friedman, A.H., Friedman, H., Gallia, G.L., Giovanella, B.C., et al. (2013). TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal. Proc Natl Acad Sci USA 110, 6021–6026.

    CAS  PubMed  Google Scholar 

  • Kim, S.J., Park, S.Y., Lee, Y.J., Lee, E.K., Kim, S.K., Kim, T.H., Jung, Y.S., Ryu, J., Myong, J.P., and Chung, K.W. (2014). Risk factors for recurrence after therapeutic lateral neck dissection for primary papillary thyroid cancer. Ann Surg Oncol 21, 1884–1890.

    PubMed  Google Scholar 

  • LaFranchi, S.H. (2015). Inaugural management guidelines for children with thyroid nodules and differentiated thyroid cancer: children are not small adults. Thyroid 25, 713–715.

    PubMed  Google Scholar 

  • Lee, J., Jeong, S., Lee, C.R., Ku, C.R., Kang, S.W., Jeong, J.J., Nam, K.H., Shin, D.Y., Chung, W.Y., Lee, E.J., et al. (2015). GLI1 transcription factor affects tumor aggressiveness in patients with papillary thyroid cancers. Medicine 94, e998.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Li, J.J., Zheng, P.C.J.R., and Wang, Y.Z. (2017). The correlations between DNA methylation and polymorphisms in the promoter region of the human telomerase reverse transcriptase (hTERT) gene with postoperative recurrence in patients with thyroid carcinoma (TC). World J Surg Onc 15, 114.

    Google Scholar 

  • Liu, C., Chen, T., and Liu, Z. (2016). Associations between BRAFV600E and prognostic factors and poor outcomes in papillary thyroid carcinoma: a meta-analysis. World J Surg Onc 14, 241.

    Google Scholar 

  • Liu, R., Bishop, J., Zhu, G., Zhang, T., Ladenson, P.W., and Xing, M. (2017). Mortality risk stratification by combining BRAF V600E and TERT promoter mutations in papillary thyroid cancer. JAMA Oncol 3, 202–208.

    PubMed  Google Scholar 

  • Liu, R., and Xing, M. (2014). Diagnostic and prognostic TERT promoter mutations in thyroid fine-needle aspiration biopsy. Endocr Relat Cancer 21, 825–830.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liu, R., and Xing, M. (2016). TERT promoter mutations in thyroid cancer. Endocr Relat Cancer 23, R143–R155.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liu, X., Bishop, J., Shan, Y., Pai, S., Liu, D., Murugan, A.K., Sun, H., El-Naggar, A.K., and Xing, M. (2013). Highly prevalent TERT promoter mutations in aggressive thyroid cancers. Endocr Relat Cancer 20, 603–610.

    PubMed  PubMed Central  Google Scholar 

  • Mercer, K.E., and Pritchard, C.A. (2003). Raf proteins and cancer: B-Raf is identified as a mutational target. BioChim Biophysica Acta (BBA) - Rev Cancer 1653, 25–40.

    CAS  Google Scholar 

  • Nikiforov, Y.E., Carty, S.E., Chiosea, S.I., Coyne, C., Duvvuri, U., Ferris, R.L., Gooding, W.E., Hodak, S.P., LeBeau, S.O., Ohori, N.P., et al. (2014). Highly accurate diagnosis of cancer in thyroid nodules with follicular neoplasm/suspicious for a follicular neoplasm cytology by ThyroSeq v2 next-generation sequencing assay. Cancer 120, 3627–3634.

    CAS  PubMed  Google Scholar 

  • Parisi, M.T., Eslamy, H., and Mankoff, D. (2016). Management of differentiated thyroid cancer in children: focus on the American Thyroid Association Pediatric Guidelines. Semin Nucl Med 46, 147–164.

    PubMed  Google Scholar 

  • Ronsley, R., Rassekh, S.R., Shen, Y., Lee, A.F., Jantzen, C., Halparin, J., Albert, C., Hawkins, D.S., Amed, S., Rothstein, R., et al. (2018). Application of genomics to identify therapeutic targets in recurrent pediatric papillary thyroid carcinoma. Cold Spring Harb Mol Case Stud 4, a002568.

    PubMed  PubMed Central  Google Scholar 

  • Schneider, D.F., and Chen, H. (2013). New developments in the diagnosis and treatment of thyroid cancer. CA Cancer J Clin 63, 373–394.

    PubMed Central  Google Scholar 

  • Shattuck, T.M., Westra, W.H., Ladenson, P.W., and Arnold, A. (2005). Independent clonal origins of distinct tumor foci in multifocal papillary thyroid carcinoma. N Engl J Med 352, 2406–2412.

    CAS  PubMed  Google Scholar 

  • Shen, Y. (2018). Next-generation sequencing based molecular testing is an equalizer for diagnostic service of rare genetic disorders in China. Pediatr Invest 2, 96–97.

    Google Scholar 

  • Shrestha, R.T., Karunamurthy, A., Amin, K., Nikiforov, Y.E., and Caramori, M.L. (2015). Multiple mutations detected preoperatively may predict aggressive behavior of papillary thyroid cancer and guide management—a case report. Thyroid 25, 1375–1378.

    CAS  PubMed  Google Scholar 

  • Siddiqui, S., White, M.G., Antic, T., Grogan, R.H., Angelos, P., Kaplan, E. L., and Cipriani, N.A. (2016). Clinical and pathologic predictors of lymph node metastasis and recurrence in papillary thyroid microcarcinoma. Thyroid 26, 807–815.

    CAS  PubMed  Google Scholar 

  • Siegel, R.L., Miller, K.D., and Jemal, A. (2017). Cancer Statistics, 2017. CA Cancer J Clin 67, 7–30.

    PubMed  Google Scholar 

  • Sigurdson, A.J., Ronckers, C.M., Mertens, A.C., Stovall, M., Smith, S.A., Liu, Y., Berkow, R.L., Hammond, S., Neglia, J.P., Meadows, A.T., et al. (2005). Primary thyroid cancer after a first tumour in childhood (the Childhood Cancer Survivor Study): a nested case-control study. Lancet 365, 2014–2023.

    PubMed  Google Scholar 

  • Su, X., Jiang, X., Wang, W., Wang, H., Xu, X., Lin, A., Teng, X., Wu, H., and Teng, L. (2016). Association of telomerase reverse transcriptase promoter mutations with clinicopathological features and prognosis of thyroid cancer: a meta-analysis. Onco Targets Ther 9, 6965–6976.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tufano, R.P., Teixeira, G.V., Bishop, J., Carson, K.A., and Xing, M. (2012). BRAF mutation in papillary thyroid cancer and its value in tailoring initial treatment. Medicine 91, 274–286.

    CAS  PubMed  Google Scholar 

  • Yu, X.M., Wan, Y., Sippel, R.S., and Chen, H. (2011). Should all papillary thyroid microcarcinomas be aggressively treated? Ann Surgery 254, 653–660.

    Google Scholar 

  • Vergamini, L.B., Frazier, A.L., Abrantes, F.L., Ribeiro, K.B., and Rodriguez-Galindo, C. (2014). Increase in the incidence of differentiated thyroid carcinoma in children, adolescents, and young adults: a population-based study. J Pediatrics 164, 1481–1485.

    Google Scholar 

  • Vuong, H.G., Altibi, A.M.A., Duong, U.N.P., and Hassell, L. (2017). Prognostic implication of BRAF and TERT promoter mutation combination in papillary thyroid carcinoma—A meta-analysis. Clin Endocrinol 87, 411–417.

    CAS  Google Scholar 

  • Wang, Y., Kowalski, J., Tsai, H.L., Marik, R., Prasad, N., Somervell, H., Lo, P.K., Sangenario, L.E., Dyrskjot, L., Orntoft, T.F., et al. (2008). Differentiating alternative splice variant patterns of human telomerase reverse transcriptase in thyroid neoplasms. Thyroid 18, 1055–1063.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, Y., Meeker, A.K., Kowalski, J., Tsai, H.L., Somervell, H., Heaphy, C., Sangenario, L.E., Prasad, N., Westra, W.H., Zeiger, M.A., et al. (2011). Telomere length is related to alternative splice patterns of telomerase in thyroid tumors. Am J Pathol 179, 1415–1424.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ward, E., DeSantis, C., Robbins, A., Kohler, B., and Jemal, A. (2014). Childhood and adolescent cancer statistics, 2014. CA A Cancer J Clin 64, 83–103.

    Google Scholar 

  • Xing, M., Liu, R., Liu, X., Murugan, A.K., Zhu, G., Zeiger, M.A., Pai, S., and Bishop, J. (2014). BRAF V600E and TERT promoter mutations cooperatively identify the most aggressive papillary thyroid cancer with highest recurrence. J Clin Oncol 32, 2718–2726.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Xing, M., Westra, W.H., Tufano, R.P., Cohen, Y., Rosenbaum, E., Rhoden, K.J., Carson, K.A., Vasko, V., Larin, A., Tallini, G., et al. (2005). BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer. J Clin Endocrinol Metab 90, 6373–6379.

    CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported in part by Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (ZYLX201508), Beijing Municipal Science and Technol¬ogy Project (D131100005313014), Beijing Health System Top Level Health Technical Personnel Training Plan (20153079), Key subjects of medical science research in Hebei Province (20170395).

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Correspondence to Yingluan Song or Xin Ni.

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Geng, J., Liu, Y., Guo, Y. et al. Correlation between TERT C228T and clinic-pathological features in pediatric papillary thyroid carcinoma. Sci. China Life Sci. 62, 1563–1571 (2019). https://doi.org/10.1007/s11427-018-9546-5

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