Frequency of TERT promoter mutations in primary tumors of the liver

Quaas, Alexander; Oldopp, Theresa; Tharun, Lars; Klingenfeld, Catina; Krech, Till; Sauter, Guido; Grob, Tobias

doi:10.1007/s00428-014-1658-7

Cited by 55 publications

(44 citation statements)

References 18 publications

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“…To date, hTERT promoter mutations have been evaluated in more than 60 tumor types and they are found to be the most common point mutations in hepatocellular carcinoma [253,254], glioblastoma [253], bladder cancer [255] and melanoma [251,252]. …”

Section: Genetic Alterations Regulating Htert Transcriptionmentioning

confidence: 99%

Transcription Regulation of the Human Telomerase Reverse Transcriptase (hTERT) Gene

Ramlee

Wang

Toh

et al. 2016

Genes

129

132

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Embryonic stem cells and induced pluripotent stem cells have the ability to maintain their telomere length via expression of an enzymatic complex called telomerase. Similarly, more than 85%–90% of cancer cells are found to upregulate the expression of telomerase, conferring them with the potential to proliferate indefinitely. Telomerase Reverse Transcriptase (TERT), the catalytic subunit of telomerase holoenzyme, is the rate-limiting factor in reconstituting telomerase activity in vivo. To date, the expression and function of the human Telomerase Reverse Transcriptase (hTERT) gene are known to be regulated at various molecular levels (including genetic, mRNA, protein and subcellular localization) by a number of diverse factors. Among these means of regulation, transcription modulation is the most important, as evident in its tight regulation in cancer cell survival as well as pluripotent stem cell maintenance and differentiation. Here, we discuss how hTERT gene transcription is regulated, mainly focusing on the contribution of trans-acting factors such as transcription factors and epigenetic modifiers, as well as genetic alterations in hTERT proximal promoter.

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Section: Genetic Alterations Regulating Htert Transcriptionmentioning

confidence: 99%

Transcription Regulation of the Human Telomerase Reverse Transcriptase (hTERT) Gene

Ramlee

Wang

Toh

et al. 2016

Genes

129

132

View full text Add to dashboard Cite

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“…The frequency of TERT promoter mutations in HCC varies substantially across the different geographical regions studied. For example, cases of HCC with TERT promoter mutations have been reported from the United States[161], Europe[104,158,162], Africa[163], and East Asia (except for Japan)[103,104,164-166], with mutation frequencies of 44%, 47%-59%, 53%, and 20.7%-38.8%, respectively. These data indicate that TERT promoter mutations are less frequent among Asian patients with HBV-related HCC than among those with HCV-related HCC.…”

Section: Somatic Mutations In Hccmentioning

confidence: 99%

Genetic alterations in hepatocellular carcinoma: An update

Niu¹,

Niu²,

Wang³

2016

WJG

130

108

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Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Although recent advances in therapeutic approaches for treating HCC have improved the prognoses of patients with HCC, this cancer is still associated with a poor survival rate mainly due to late diagnosis. Therefore, a diagnosis must be made sufficiently early to perform curative and effective treatments. There is a need for a deeper understanding of the molecular mechanisms underlying the initiation and progression of HCC because these mechanisms are critical for making early diagnoses and developing novel therapeutic strategies. Over the past decade, much progress has been made in elucidating the molecular mechanisms underlying hepatocarcinogenesis. In particular, recent advances in next-generation sequencing technologies have revealed numerous genetic alterations, including recurrently mutated genes and dysregulated signaling pathways in HCC. A better understanding of the genetic alterations in HCC could contribute to identifying potential driver mutations and discovering novel therapeutic targets in the future. In this article, we summarize the current advances in research on the genetic alterations, including genomic instability, single-nucleotide polymorphisms, somatic mutations and deregulated signaling pathways, implicated in the initiation and progression of HCC. We also attempt to elucidate some of the genetic mechanisms that contribute to making early diagnoses of and developing molecularly targeted therapies for HCC.

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“…Thus, immortality associated with cancer cells has been thought to be caused by telomerase overexpression. Importantly, the newly described germline and recurrent somatic mutations in melanoma (35) and other cancers (36) in the TERT promoter that create de novo ETS/TCF binding sites, provide an insight into the possible cause of tumor-specific increased TERT expression (32, 33, 37). …”

Section: Introductionmentioning

confidence: 99%

Aberrant expression of ETS1 and ETS2 proteins in cancer

Fry

Inoue

2018

Cancer Rep Rev

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The ETS transcription factors regulate expression of genes involved in normal cell development, proliferation, differentiation, angiogenesis, and apoptosis, consisting of 28 family members in humans. Dysregulation of these transcription factors facilitates cell proliferation in cancers, and several members participate in invasion and metastasis by activating gene transcription. ETS1 and ETS2 are the founding members of the ETS family and regulate transcription by binding to ETS sequences. They are both involved in oncogenesis and tumor suppression depending on the biological situations used. The essential roles of ETS proteins in human telomere maintenance have been suggested, which have been linked to creation of new Ets binding sites. Recently, preferential binding of ETS2 to gain-of-function mutant p53 and ETS1 to wild type p53 (WTp53) has been suggested, raising the tumor promoting role for the former and tumor suppressive role for the latter. The oncogenic and tumor suppressive functions of ETS1 and 2 proteins have been discussed.

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Frequency of TERT promoter mutations in primary tumors of the liver

Cited by 55 publications

References 18 publications

Transcription Regulation of the Human Telomerase Reverse Transcriptase (hTERT) Gene

Transcription Regulation of the Human Telomerase Reverse Transcriptase (hTERT) Gene

Genetic alterations in hepatocellular carcinoma: An update

Aberrant expression of ETS1 and ETS2 proteins in cancer

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