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TERT promoter mutation as an early genetic event activating telomerase in follicular thyroid adenoma (FTA) and atypical FTA.
Cancer. 2014 Oct 01; 120(19):2965-79.C

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

TERT promoter mutations may occur as an early genetic event in thyroid follicular tumors that have not developed malignant features on routine histopathological workup.

Authors+Show Affiliations

Department of Oncology-Pathology and Cancer Center Karolinska, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24898513

Citation

Wang, Na, et al. "TERT Promoter Mutation as an Early Genetic Event Activating Telomerase in Follicular Thyroid Adenoma (FTA) and Atypical FTA." Cancer, vol. 120, no. 19, 2014, pp. 2965-79.
Wang N, Liu T, Sofiadis A, et al. TERT promoter mutation as an early genetic event activating telomerase in follicular thyroid adenoma (FTA) and atypical FTA. Cancer. 2014;120(19):2965-79.
Wang, N., Liu, T., Sofiadis, A., Juhlin, C. C., Zedenius, J., Höög, A., Larsson, C., & Xu, D. (2014). TERT promoter mutation as an early genetic event activating telomerase in follicular thyroid adenoma (FTA) and atypical FTA. Cancer, 120(19), 2965-79. https://doi.org/10.1002/cncr.28800
Wang N, et al. TERT Promoter Mutation as an Early Genetic Event Activating Telomerase in Follicular Thyroid Adenoma (FTA) and Atypical FTA. Cancer. 2014 Oct 1;120(19):2965-79. PubMed PMID: 24898513.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TERT promoter mutation as an early genetic event activating telomerase in follicular thyroid adenoma (FTA) and atypical FTA. AU - Wang,Na, AU - Liu,Tiantian, AU - Sofiadis,Anastasios, AU - Juhlin,C Christofer, AU - Zedenius,Jan, AU - Höög,Anders, AU - Larsson,Catharina, AU - Xu,Dawei, Y1 - 2014/06/04/ PY - 2013/11/27/received PY - 2014/03/31/revised PY - 2014/04/03/accepted PY - 2014/6/6/entrez PY - 2014/6/6/pubmed PY - 2014/11/8/medline KW - TERT promoter mutation KW - atypical follicular thyroid adenoma KW - benign entity KW - follicular thyroid adenoma KW - follicular thyroid carcinoma KW - telomerase SP - 2965 EP - 79 JF - Cancer JO - Cancer VL - 120 IS - 19 N2 - BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: TERT promoter mutations may occur as an early genetic event in thyroid follicular tumors that have not developed malignant features on routine histopathological workup. SN - 1097-0142 UR - https://www.unboundmedicine.com/medline/citation/24898513/TERT_promoter_mutation_as_an_early_genetic_event_activating_telomerase_in_follicular_thyroid_adenoma__FTA__and_atypical_FTA_ L2 - https://doi.org/10.1002/cncr.28800 DB - PRIME DP - Unbound Medicine ER -