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TERT mRNA Expression as a Novel Prognostic Marker in Papillary Thyroid Carcinomas

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Title: TERT mRNA Expression as a Novel Prognostic Marker in Papillary Thyroid Carcinomas
Authors: Tanaka, Aya / Matsuse, Michiko / Saenko, Vladimir / Nakao, Tomoe / Yamanouchi, Kosho / Sakimura, Chika / Yano, Hiroshi / Nishihara, Eijun / Hirokawa, Mitsuyoshi / Suzuki, Keiji / Miyauchi, Akira / Eguchi, Susumu / Yoshiura, Ko-ichiro / Yamashita, Shunichi / Nagayasu, Takeshi / Mitsutake, Norisato
Issue Date: 19-Aug-2019
Publisher: Mary Ann Liebert, Inc.
Citation: Thyroid, 29(8), pp.1105-1114; 2019
Abstract: Telomerase reverse transcriptase (TERT) promoter mutations have been found in a subset of papillary thyroid carcinomas (PTCs) and are associated with tumor aggressiveness and worse prognosis. However, little is known about the status of TERT mRNA expression and its relationship between TERT promoter mutations and clinicopathological features. Methods: We analyzed 159 PTC samples for TERT promoter mutations using direct DNA sequencing. TERT expression was measured using quantitative reverse transcription polymerase chain reaction. To examine low allelic frequency of TERT promoter mutations with high sensitivity, we used droplet digital polymerase chain reaction (ddPCR). The relationship between the status of the TERT promoter mutation/expression and clinicopathological features including recurrence risk was statistically analyzed. Results: TERT promoter mutations were found in 20 cases (12.6%). However, TERT expression was observed not only in the mutation-positive tumors but also in 56 of 139 (40.3%) mutation-negative tumors. Among them, we detected low allelic frequency of TERT promoter mutations in three samples (5.4%) using ddPCR. We confirmed a significant association between TERT promoter mutations and aggressive clinicopathological features in this series. The risk of recurrence of TERT mutation-negative/expression-positive tumors was significantly higher than that of the mutation-negative/expression-negative tumors, suggesting that TERT expression even in absence of a mutation confers a negative influence on PTCs. Moreover, when we reclassified the mutation-negative cases into two groups based on the TERT expression levels: expression-negative/expression levels <80th percentile and expression levels >80th percentile because minimal expression may have a negligible clinical impact, a higher hazard ratio for recurrence was observed. Interestingly, TERT expression levels in the mutation-negative PTCs were inversely correlated with patient age and the presence of BRAF mutations. Conclusions: We confirm a strong correlation between the presence of TERT promoter mutations and aggressive clinicopathological features in this PTC series. In addition, there were PTCs showing high TERT mRNA expression even in the absence of TERT promoter mutations. These cases also showed a significantly higher recurrence rate. Since the TERT promoter mutations are observed only in elderly patients, TERT mRNA expression can be a useful prognostic marker especially in younger PTC patients.
Keywords: papillary thyroid carcinoma / prognostic marker / TERT / TERT expression / TERT promoter mutation
URI: http://hdl.handle.net/10069/39431
ISSN: 10507256
DOI: 10.1089/thy.2018.0695
Rights: © 2019 Mary Ann Liebert, Inc., publishers. Final publication is available from Mary Ann Liebert, Inc., publishers http://dx.doi.org/10.1089/thy.2018.0695
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/39431

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