Telomerase in differentiated thyroid cancer: Promoter mutations, expression and localization

Muzza, Marina; Colombo, Carla; Rossi, Stefania; Tosi, Delfina; Cirello, Valentina; Perrino, Michela; Leo, Simone De; Magnani, Elisa; Pignatti, Elisa; Vigo, Beatrice; Simoni, Manuela; Bulfamante, Gaetano; Vicentini, Leonardo; Fugazzola, Laura

doi:10.1016/j.mce.2014.10.019

Cited by 102 publications

(139 citation statements)

References 35 publications

(44 reference statements)

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“…In our study, the prevalence of TERT promoter mutations in CPTC was relatively low (6.5%). Other studies showed rates that ranged between 4.5 and 22.5%, with most studies showing a frequency of TERT promoter mutations of around 12% in CPTC (Landa et al 2013, Liu et al 2013, Vinagre et al 2013, Gandolfi et al 2015, Muzza et al 2015. Similar to previous studies, ours showed TERT promoter mutations in 8/57 (14%) cases of FVPTC.…”

Section: Discussionsupporting

confidence: 89%

“…However, the relative significance of each of those features varies among these studies. A consistent finding is that TERT promoter mutations occur more frequently at an older age and are associated with distant metastasis, higher tumor stage and poorly differentiated types of TC (Vinagre et al 2013, Gandolfi et al 2015, Muzza et al 2015, Shi et al 2015. Interestingly, tumor size, extrathyroidal invasion, tumor multifocality, lymph node metastasis and vascular invasion are not consistently associated with TERT promoter mutations.…”

Section: Discussionmentioning

confidence: 82%

“…This is consistent with previous studies. In six previous studies that included 476 benign thyroid tumors of different types, none was found to harbor TERT promoter mutations (Liu et al 2013, Vinagre et al 2013, Muzza et al 2015. However, in one study, one out of 58 benign follicular adenomas and three of 18 atypical follicular adenomas harbored C228T TERT promoter mutation, suggesting that this mutation is an early molecular event in thyroid tumorigenesis .…”

Section: Discussionmentioning

confidence: 87%

“…BRAF V600E mutation was more frequent in cases with C228T mutations than in those without mutation. Several subsequent studies from North America and Europe showed that TERT promoter mutations occurred in about 10-15% TCs (Landa et al 2013, Vinagre et al 2013, Fredriksson et al 2014,b, Gandolfi et al 2015, Muzza et al 2015, Shi et al 2015. These mutations were more common in the poorly differentiated and anaplastic TC and were associated with more aggressive features of DTC (Landa et al 2013, Liu et al 2013.…”

Section: Discussionmentioning

confidence: 96%

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TERT promoter mutations in thyroid cancer: a report from a Middle Eastern population

Qasem¹,

Murugan²,

Al‐Hindi³

et al. 2015

Endocrine-Related Cancer

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Telomerase reverse transcriptase (TERT) promoter mutations C228T and C250T have recently been described in follicular cell-derived thyroid cancer (TC) in patients from North America and Europe. In this study, we explored whether these findings could be replicated in patients from a different ethnic group. We screened 17 benign thyroid adenomas and 265 TC samples from patients in the Middle East for these mutations by PCR and direct sequencing using DNA isolated from paraffin-embedded tumor tissues. None of the 17 benign adenomas harbored TERT promoter mutations. Of 265 TC, 34 (12.8%) harbored TERT promoter mutations, including 10/153 (6.5%) conventional papillary TC (CPTC), 8/57 (14.0%) follicular variant PTC, 9/30 (30%) tall cell variant PTC, 1/3 (30%) Hurthle cell thyroid cancer (HTC), 1/5 (20%) follicular TC, and 5/13 (38.5%) poorly differentiated TC. C250T mutation was present in only 6/265 (2.3%) cases, while C228T mutation was present in a total of 28/265 (10.6%) cases. These two mutations were mutually exclusive. TERT promoter mutations were significantly more common in older (R45 years) than younger patients and were associated with larger tumour size, vascular invasion, higher TNM stage (stage III and IV), BRAF V600E mutation and persistent/recurrent disease at 6-12 months after initial treatment and at the last follow up. These associations were stronger in non-CPTC. Thus, this study on a large cohort of TC patients from Middle East demonstrates that TERT promoter mutations are relatively common, especially in the non-CPTC, and are associated with more aggressive histopathological features, BRAF V600E mutation, and disease persistence/recurrence than the WT TERT.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 96%

See 2 more Smart Citations

TERT promoter mutations in thyroid cancer: a report from a Middle Eastern population

Qasem¹,

Murugan²,

Al‐Hindi³

et al. 2015

Endocrine-Related Cancer

View full text Add to dashboard Cite

show abstract

“…In our series, no differences in Tert IHC staining were observed between TERT-mutated and TERT-wild type tumors, in accordance with a recent study [32]. This finding suggests that molecular mechanisms distinct from promoter mutations may contribute to telomerase activation in lung cancer.…”

Section: Discussionsupporting

confidence: 93%

TERT Promoter Mutations and Tert Expression in Early-Stage (T1N0M0) Non-Small Cell Lung Cancer (NSCLC)

Giordano¹,

Macerola²,

Boldrini³

et al. 2015

J Clin Exp Pathol

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Background: The mutations detected in the promoter of the telomerase reverse transcriptase (TERT) gene, namely C228T and C250T, were first identified in melanoma and subsequently in several cancer models, notably glioma, thyroid cancer and bladder cancer. Recent findings demonstrate that mutation of the TERT promoter may be one of the most common genetic mechanisms contributing to telomerase activation in malignant cells. Mutation of the TERT promoter appears to be an indicator of worse outcome and is correlated with tumor aggressiveness and patient survival; however, to date the only two published studies reported a very low TERT mutation frequency in non-small cell lung cancer (NSCLC). Additionally, the relationship among the presence of these mutations, Tert expression and clinical outcome is unknown.

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IGSF1: A novel oncogene regulates the thyroid cancer progression

Guan

Wang

Bhandari

et al. 2019

Cell Biochemistry & Function

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Thyroid cancer has been continuously increasing and extraordinarily prevalent worldwide. The genetic diagnosis has been widely used in fine needle aspiration. IGSF1, an immunoglobulin superfamily member 1, has been shown to be associated with the regulation of thyroid hormone. But the function of IGSF1 in thyroid cancer has not been explored yet. In this article, we will illuminate the correlation between IGSF1 expression and thyroid cancer. We analysed the level of IGSF1 expression in 55 pairs of tissue samples by real‐time polymerase chain reaction (PCR) and The Cancer Genome Atlas (TCGA) data portal. After that, we transfected small interfering RNA to silence IGSF1 in thyroid cancer cell lines (KTC‐1 and BCPAP) and confirmed the function of IGSF1 by performed colony formation, migration, invasion, cell counting kit‐8, and apoptosis assays. IGSF1 was upregulated in thyroid cancer tissues compared with the adjacent normal tissues (t = 5.783, df = 54; P < .0001) and TCGA (T: N = 65.91 ± 3.998, n = 501: 2.824 ± 0.273, n = 58; P < .0001). In thyroid cell lines, experiments showed that downregulated IGSF1 inhibited proliferation, metastasis, and promoted cell apoptosis. Meanwhile, inhibited IGSF1 expression could downregulate N‐cadherin, vimentin, and EZH2, which is associated with metastasis. Thyroid cancer cells IGSF1 expression levels are a correlation with its ability to growth, metastasis, and apoptosis.

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Telomerase in differentiated thyroid cancer: Promoter mutations, expression and localization

Cited by 102 publications

References 35 publications

TERT promoter mutations in thyroid cancer: a report from a Middle Eastern population

TERT promoter mutations in thyroid cancer: a report from a Middle Eastern population

TERT Promoter Mutations and Tert Expression in Early-Stage (T1N0M0) Non-Small Cell Lung Cancer (NSCLC)

IGSF1: A novel oncogene regulates the thyroid cancer progression

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