Erratum to: TERT promoter hot spot mutations are frequent in Indian cervical and oral squamous cell carcinomas

Vinothkumar, Vilvanathan; Arunkumar, Ganesan; Revathidevi, Sundaramoorthy; Arun, Kanagaraj; Manikandan, Mayakannan; Rao, Arunagiri Kuha Deva Magendhra; Seenivasagam, Rajkumar Kottayasamy; Ajay, Chandrasekar; Rajaraman, Ramamurthy; Ramani, Rajendren; Murugan, Avaniyapuram Kannan; Munirajan, Arasambattu Kannan

doi:10.1007/s13277-016-4829-0

Cited by 1 publication

(5 citation statements)

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“…Likewise, TERTp mutations are generally absent from cancers where telomere elongation is ensured by ALT [77,79,80,98] or TERT copy-number duplications [38,121]. TERTp mutations are also less frequent in cancers where viral transformation or viral oncogenes reactivate TERT transcription, such as HBV-DNA or high-risk HPV16/18 E6 [30,32,33,36,37,62,95,96,121,122]. These observations reinforce the concept that, despite some exceptions [38,89,111,117], tumors generally rely on one mechanism for telomere maintenance.…”

Section: Exclusiveness Of Tertp Mutationssupporting

confidence: 57%

“…TERTp mutations were detected in cervical SCC (20.1%, range 4.5-21.8%) and HNSCC (22.5%, range 17-31.7%) [36,37]. These malignancies are often associated with high-risk-HPV16/18 E6 and E7 viral oncoproteins and with APOBEC mutations [125][126][127].…”

Section: Cervical and Oral Head And Neck Squamous Cell Carcinoma (Hnscc)mentioning

confidence: 99%

“…TERTp mutations have a notably higher prevalence in HPV-negative cervical and oral SCC. This gives distinct patterns of TERT reactivation through mutually exclusive mechanisms [36,37]. In cervical SCC, they are associated with higher TERT levels than HPV16/18-E6-positive tumors and with advanced cervical cancer [36,37].…”

Section: Cervical and Oral Head And Neck Squamous Cell Carcinoma (Hnscc)mentioning

confidence: 99%

“…This gives distinct patterns of TERT reactivation through mutually exclusive mechanisms [36,37]. In cervical SCC, they are associated with higher TERT levels than HPV16/18-E6-positive tumors and with advanced cervical cancer [36,37]. Broader studies are needed to evaluate the added value of screening for the molecular mechanism underlying TERT reactivation in cervical and oral SCC.…”

Section: Cervical and Oral Head And Neck Squamous Cell Carcinoma (Hnscc)mentioning

confidence: 99%

“…The TERT promoter (TERTp) contains binding sites for numerous transcriptional activators including Sp-1, c-Myc, Hypoxia Induced Factor (HIF), AP-2, β-catenin, NF-κB, E-twenty-six (Ets)/ternary complex factors (TCF) family members, and transcriptional repressors (Wilms' tumor (WT1), TP53, Nuclear Transcription Factor, X-Box Binding (NFX-1), Mad-1 and CCCTC binding factor (CTCF)) [3,4,9,[17][18][19][20][21]29]. TERT expression can be reactivated reactivated by copy number variants (CNV), TERT or TERTp structural variants, chromosomal rearrangements juxtaposing TERTp to enhancer elements, cellular and viral oncogenes such as Hepatitis B virus (HBV) X protein (HBx) or high-risk Human papillomavirus (HPV) 16 and HPV18 E6 oncoprotein, and, last but not least, mutations within TERTp (31% of TERT-expressing cancers) ( Figure 1A) [10,[30][31][32][33][34][35][36][37][38] (reviewed in [3,4,9,[18][19][20]39]). Increased TERTp methylation is typically recorded in >50% of TERT-expressing tumors and cell lines [10,[40][41][42][43][44][45][46][47].…”

Section: Introductionmentioning

confidence: 99%

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The Solo Play of TERT Promoter Mutations

Hafezi

Perez-Bercoff

2020

Cells

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The reactivation of telomerase reverse transcriptase (TERT) protein is the principal mechanism of telomere maintenance in cancer cells. Mutations in the TERT promoter (TERTp) are a common mechanism of TERT reactivation in many solid cancers, particularly those originating from slow-replicating tissues. They are associated with increased TERT levels, telomere stabilization, and cell immortalization and proliferation. Much effort has been invested in recent years in characterizing their prevalence in different cancers and their potential as biomarkers for tumor stratification, as well as assessing their molecular mechanism of action, but much remains to be understood. Notably, they appear late in cell transformation and are mutually exclusive with each other as well as with other telomere maintenance mechanisms, indicative of overlapping selective advantages and of a strict regulation of TERT expression levels. In this review, we summarized the latest literature on the role and prevalence of TERTp mutations across different cancer types, highlighting their biased distribution. We then discussed the need to maintain TERT levels at sufficient levels to immortalize cells and promote proliferation while remaining within cell sustainability levels. A better understanding of TERT regulation is crucial when considering its use as a possible target in antitumor strategies.Cells 2020, 9, 749 2 of 28 by copy number variants (CNV), TERT or TERTp structural variants, chromosomal rearrangements juxtaposing TERTp to enhancer elements, cellular and viral oncogenes such as Hepatitis B virus (HBV) X protein (HBx) or high-risk Human papillomavirus (HPV)16 and HPV18 E6 oncoprotein, and, last but not least, mutations within TERTp (31% of TERT-expressing cancers) ( Figure 1A) [10, 30-38] (reviewed in [3,4,9,18-20,39]). Increased TERTp methylation is typically recorded in >50% of TERT-expressing tumors and cell lines [10,[40][41][42][43][44][45][46][47]. Epigenetic regulation of TERTp is based on altered methylation patterns of specific regions. Hypomethylation of the region between −200 and −100 from the Translational Start site (TSS), encompassing the core promoter, enables binding of c-Myc and Sp-1, thus reactivating transcription. In contrast, the region spanning exon 1 (positions +1 to ±100 from the TSS) contains a binding site for the DNA insulator CTCF. Hypermethylation of this region disrupts binding of CTCF and therefore allows TERT transcription [41][42][43][44]. Similarly, the region between −600 and −200 from the TSS contains a second CTCF binding site and is partially hypermethylated in TERT-expressing cells [41][42][43][44].

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