TERT promoter mutation in resectable hepatocellular carcinomas: A strong association with hepatitis C infection and absence of hepatitis B infection

Chen, Yuling; Jeng, Yung‐Ming; Chang, Cheng-Chi; Lee, Hsin‐Jung; Hsu, Hey‐Chi; Lai, Po-Lin; Yuan, Ray-Hwang

doi:10.1016/j.ijsu.2014.05.066

Cited by 65 publications

(78 citation statements)

References 30 publications

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“…Specifically, they were observed in 57% of preneoplastic lesions and in 30% of stage I HCCs[165], indicating that TERT promoter mutations occur early during malignant transformation and persist throughout tumor progression. These findings have been further confirmed by two recent studies using exome or DNA sequencing of liver tumor samples in which TERT promoter mutations occurred early during hepatocarcinogenesis[106,164]. In addition, when hTERT mRNA was measured via real-time quantitative RT-PCR, the hTERT mRNA levels were found to be increased in association with the progression of hepatocarcinogenesis, and most HGDNs strongly expressed hTERT mRNA at levels similar to those in HCC samples[168].…”

Section: Somatic Mutations In Hccmentioning

confidence: 59%

“…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%

“…The lower rate of TERT promoter mutations in patients with HBV-related HCC might be partially explained by the frequent insertion of HBV DNA in the TERT promoter, which is known to induce telomerase transcription[103,155]. These findings suggest that various etiological factors could be involved in different mechanisms that preserve telomeres during the carcinogenesis of HCC[164]. Despite these differences, TERT promoter mutations are currently considered the most frequent somatic genetic alterations in HCC regardless of patients’ geographical origin[163,167].…”

Section: Somatic Mutations In Hccmentioning

confidence: 99%

See 2 more Smart Citations

Genetic alterations in hepatocellular carcinoma: An update

Niu¹,

Niu²,

Wang³

2016

WJG

131

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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Section: Somatic Mutations In Hccmentioning

confidence: 59%

Section: Somatic Mutations In Hccmentioning

confidence: 99%

Section: Somatic Mutations In Hccmentioning

confidence: 99%

See 1 more Smart Citation

Genetic alterations in hepatocellular carcinoma: An update

Niu¹,

Niu²,

Wang³

2016

WJG

131

108

View full text Add to dashboard Cite

show abstract

“…Following stratification of variables, including TL, TERT promoter mutation status exhibited no prognostic significance (data not shown). Certain recent studies demonstrated no difference in TERT expression compared with the presence of TERT promoter mutations (21,22). These reports indicate that tumor cells without TERT promoter mutations may have other mechanisms for activating TERT expression and changing TL.…”

Section: Tert Promoter Status ---------------------------------------mentioning

confidence: 79%

Mutation of the TERT promoter leads to poor prognosis of patients with non-small cell lung cancer

et al. 2017

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Abstract. Mutations in the promoter region of telomerase reverse transcriptase (TERT) and alterations in telomere length (TL) have been the focus of research in various types of cancer. In the present study, the frequency and clinical characteristics of TERT promoter mutations and TL were studied in non-small cell lung cancers (NSCLC). TERT promoter mutations and TL were analyzed in 188 patients using DNA sequencing and the reverse transcription-quantitative polymerase chain reaction, respectively. The TERT promoter mutation rate was observed to be 2.2% (4/188 NSCLC cases), and it was significantly associated with regional lymph node invasion (P<0.001). No significant difference in TL was observed between the patients with and without TERT promoter mutations. TL was decreased in males (P=0.058 vs. females) and smokers (P=0.008 vs. non-smokers). Survival analyses demonstrated poor prognoses for patients with NSCLC with TERT promoter mutations (P<0.001). Multivariate survival analyses demonstrated that TERT promoter mutations were an independent prognostic marker for poor overall survival (P=0.045). The results of the present study demonstrated that TERT promoter mutation was not frequent in NSCLC; however, it may have value as a prognostic marker in NSCLC.

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“…Preferential integration of the HBV genome in the regions near or in the TERT gene has also been reported in five of the six HBV-HCC NGS studies [16,19,108–110]. Interestingly, higher rates of mutations in TERT (46% in HCV-HCC vs 16% in HBV-HCC) [111] and CTNNB1 (62.5% in HCV-HCC vs 37.5% in non-HCV-HCC) [15] were reported in HCV-associated HCC. Recently, it was suggested that TERT is the gate keeper of HCC [112].…”

Section: Hcc-associated Cancer Pathways and Candidate Dna Biomarkers Fomentioning

confidence: 87%

DNA markers in molecular diagnostics for hepatocellular carcinoma

Lin

Song

et al. 2014

Expert Review of Molecular Diagnostics

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Hepatocellular carcinoma (HCC) is the one of the leading causes of cancer mortality in the world, mainly due to the difficulty of early detection and limited therapeutic options. The implementation of HCC surveillance programs in well-defined, high-risk populations were only able to detect about 40–50% of HCC at curative stages (Barcelona Clinic Liver Cancer stages 0 & 1) due to the low sensitivities of the current screening methods. The advance of sequencing technologies has identified numerous modifications as potential candidate DNA markers for diagnosis/surveillance. Here we aim to provide an overview of the DNA alterations that result in activation of cancer pathways known to potentially drive HCC carcinogenesis and to summarize performance characteristics of each DNA marker in the periphery (blood or urine) for HCC screening.

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TERT promoter mutation in resectable hepatocellular carcinomas: A strong association with hepatitis C infection and absence of hepatitis B infection

Cited by 65 publications

References 30 publications

Genetic alterations in hepatocellular carcinoma: An update

Genetic alterations in hepatocellular carcinoma: An update

Mutation of the TERT promoter leads to poor prognosis of patients with non-small cell lung cancer

DNA markers in molecular diagnostics for hepatocellular carcinoma

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