The first 2 authors contributed equally to this work.
TERT promoter mutation as an early genetic event activating telomerase in follicular thyroid adenoma (FTA) and atypical FTA
Version of Record online: 4 JUN 2014
© 2014 American Cancer Society
Volume 120, Issue 19, pages 2965–2979, October 1, 2014
How to Cite
Wang, N., Liu, T., Sofiadis, A., Juhlin, C. C., Zedenius, J., Höög, A., Larsson, C. and Xu, D. (2014), TERT promoter mutation as an early genetic event activating telomerase in follicular thyroid adenoma (FTA) and atypical FTA. Cancer, 120: 2965–2979. doi: 10.1002/cncr.28800
We thank Prof. Emeritus Lars Grimelius for diagnostic work and Ms. Lisa Ånfalk for technical assistance in collection of the samples.
- Issue online: 19 SEP 2014
- Version of Record online: 4 JUN 2014
- Manuscript Accepted: 3 APR 2014
- Manuscript Revised: 31 MAR 2014
- Manuscript Received: 27 NOV 2013
- atypical follicular thyroid adenoma;
- follicular thyroid adenoma;
- benign entity;
- follicular thyroid carcinoma;
- TERT promoter mutation;
The telomerase reverse transcriptase (TERT) promoter mutations C228T and C250T have been found in many malignancies, including in thyroid carcinomas. However, it is unclear how early these mutations occur in thyroid tumorigenesis.
The study included primary tumors from 58 patients initially diagnosed with follicular thyroid adenoma (FTA), a benign entity, 18 with atypical FTA (AFTA) having an uncertain malignant potential, and 52 with follicular thyroid carcinoma (FTC). Sanger sequencing was used to investigate the mutational status of the TERT promoter. Telomere length and TERT messenger RNA (mRNA) expression were determined using quantitative polymerase chain reaction (PCR). Telomerase activity was assessed using a Telomerase PCR enzyme-linked immunosorbent assay kit.
The C228T mutation was identified in 1 of 58 FTA (2%) and 3 of 18 AFTA (17%) samples. These 4 tumors all expressed TERT mRNA and telomerase activity, whereas the majority of C228T-negative adenomas lacked TERT expression (C228T versus wild-type, P = .008). The C228T mutation was associated with NRAS gene mutations (P = .016). The patient with C228T-mutated FTA later developed a scar recurrence and died of FTC, whereas none of the remaining 57 patients with FTA had recurrence. No recurrence occurred in 3 patients with AFTA who carried C228T during the follow-up period (36-285 months). Nine of the 52 FTCs (17%) exhibited the TERT mutation (8 of 9 C228T and 1 of 9 C250T), and the presence of the mutation was associated with shorter patient survival.
TERT promoter mutations may occur as an early genetic event in thyroid follicular tumors that have not developed malignant features on routine histopathological workup. Cancer 2014;120:2965–2979. © 2014 American Cancer Society.