Cancer Res Treat.  2016 Jul;48(3):942-947. 10.4143/crt.2015.362.

TERT Promoter Mutations and Tumor Persistence/Recurrence in Papillary Thyroid Cancer

• Myung JK
• Kwak BK
• Lim JA
• Lee MC
• Kim MJ

• KMID: 2344066
• DOI: http://doi.org/10.4143/crt.2015.362

Abstract

PURPOSE
A telomerase reverse transcriptase (TERT) promoter mutation was identified in thyroid cancer. This TERT promoter mutation is thought to be a prognostic molecular marker, because its association with tumor aggressiveness, persistence/recurrence, and disease-specific mortality in papillary thyroid carcinoma (PTC) has been reported. In this study, we attempted to determine whether the impact of the TERT promoter mutation on PTC persistence/recurrence is independent of clinicopathological parameters.
MATERIALS AND METHODS
Using propensity score matching, 39 patients with PTC persistence or recurrence were matched with 35 patients without persistence or recurrence, with a similar age, sex, tumor size, multifocality, bilaterality, extrathyroidal extension, and lymph node metastasis. The TERT promoter and the BRAF V600E mutations were identified from PTC samples.
RESULTS
The TERT promoter mutation was detected in 18% of PTC patients (13/74). No significant difference in the frequency of the TERT promoter mutation was observed between the persistence/recurrence group and the non-recurrence group.
CONCLUSION
These results suggest that the prognostic implications of the TERT promoter mutation are dependent on clinicopathological parameters.

Keyword

Papillary thyroid cancer; Telomerase; Thyroid neoplasms

MeSH Terms

Humans
Lymph Nodes
Mortality
Neoplasm Metastasis
Propensity Score
Recurrence
Telomerase
Thyroid Gland*
Thyroid Neoplasms*
Telomerase

Reference

References

1. Smekalova EM, Shubernetskaya OS, Zvereva MI, Gromenko EV, Rubtsova MP, Dontsova OA. Telomerase RNA biosynthesis and processing. Biochemistry (Mosc). 2012; 77:1120–8.

2. Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, et al. Specific association of human telomerase activity with immortal cells and cancer. Science. 1994; 266:2011–5.

3. Clark GM, Osborne CK, Levitt D, Wu F, Kim NW. Telomerase activity and survival of patients with node-positive breast cancer. J Natl Cancer Inst. 1997; 89:1874–81.

4. Huang FW, Hodis E, Xu MJ, Kryukov GV, Chin L, Garraway LA. Highly recurrent TERT promoter mutations in human melanoma. Science. 2013; 339:957–9.

5. Soares P, Lima J, Preto A, Castro P, Vinagre J, Celestino R, et al. Genetic alterations in poorly differentiated and undifferentiated thyroid carcinomas. Curr Genomics. 2011; 12:609–17.

6. Matthews P, Jones CJ, Skinner J, Haughton M, de Micco C, Wynford-Thomas D. Telomerase activity and telomere length in thyroid neoplasia: biological and clinical implications. J Pathol. 2001; 194:183–93.

7. Capezzone M, Cantara S, Marchisotta S, Busonero G, Formichi C, Benigni M, et al. Telomere length in neoplastic and nonneoplastic tissues of patients with familial and sporadic papillary thyroid cancer. J Clin Endocrinol Metab. 2011; 96:E1852–6.

8. Liu X, Bishop J, Shan Y, Pai S, Liu D, Murugan AK, et al. Highly prevalent TERT promoter mutations in aggressive thyroid cancers. Endocr Relat Cancer. 2013; 20:603–10.

9. Landa I, Ganly I, Chan TA, Mitsutake N, Matsuse M, Ibrahimpasic T, et al. Frequent somatic TERT promoter mutations in thyroid cancer: higher prevalence in advanced forms of the disease. J Clin Endocrinol Metab. 2013; 98:E1562–6.

10. Liu X, Qu S, Liu R, Sheng C, Shi X, Zhu G, 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:E1130–6.

11. Melo M, da Rocha AG, Vinagre J, Batista R, Peixoto J, Tavares C, et al. TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas. J Clin Endocrinol Metab. 2014; 99:E754–65.

12. Liu T, Wang N, Cao J, Sofiadis A, Dinets A, Zedenius J, et al. The age- and shorter telomere-dependent TERT promoter mutation in follicular thyroid cell-derived carcinomas. Oncogene. 2014; 33:4978–84.

13. Xing M, Liu R, Liu X, Murugan AK, Zhu G, Zeiger MA, et al. BRAF V600E and TERT promoter mutations cooperatively identify the most aggressive papillary thyroid cancer with highest recurrence. J Clin Oncol. 2014; 32:2718–26.

14. Xing M, Alzahrani AS, Carson KA, Viola D, Elisei R, Bendlova B, et al. Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer. JAMA. 2013; 309:1493–501.

15. Xing M, Alzahrani AS, Carson KA, Shong YK, Kim TY, Viola D, et al. Association between BRAF V600E mutation and recurrence of papillary thyroid cancer. J Clin Oncol. 2015; 33:42–50.

16. Blasco MA. Telomere length, stem cells and aging. Nat Chem Biol. 2007; 3:640–9.

17. Canela A, Vera E, Klatt P, Blasco MA. High-throughput telomere length quantification by FISH and its application to human population studies. Proc Natl Acad Sci U S A. 2007; 104:5300–5.

18. de Biase D, Gandolfi G, Ragazzi M, Eszlinger M, Sancisi V, Gugnoni M, et al. TERT promoter mutations in papillary thyroid microcarcinomas. Thyroid. 2015; 25:1013–9.

19. Xing M. BRAF mutation in thyroid cancer. Endocr Relat Cancer. 2005; 12:245–62.

20. Xing M, Westra WH, Tufano RP, Cohen Y, Rosenbaum E, Rhoden KJ, et al. BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer. J Clin Endocrinol Metab. 2005; 90:6373–9.

21. Kim TH, Park YJ, Lim JA, Ahn HY, Lee EK, Lee YJ, et al. The association of the BRAF(V600E) mutation with prognostic factors and poor clinical outcome in papillary thyroid cancer: a meta-analysis. Cancer. 2012; 118:1764–73.