Next-Generation Sequencing of Circulating Tumor DNA Reveals Frequent Alterations in Advanced Hepatocellular Carcinoma

Ikeda, Sadakatsu; Tsigelny, Igor F.; Skjevik, Åge A.; Kono, Yuko; Mendler, Michel; Kuo, Alexander; Sicklick, Jason K.; Heestand, Gregory M.; Banks, Kimberly C.; Talasaz, AmirAli; Lanman, Richard B.; Lippman, Scott M.; Kurzrock, Razelle

doi:10.1634/theoncologist.2017-0479

Cited by 67 publications

(70 citation statements)

References 44 publications

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“…There is also accumulating evidence that NB interferes with the interaction of Hsp90 with other clients, notably ErbB2, Raf1, and v-Src, which have been reported to play a critical regulatory role in HCC progression. (44,45) In summary, our study of the Hsp90α/Bclaf1/c-Myc dependence pathway that facilitates HCC proliferation might suggest a means for treating HCC using C-terminal inhibitors of Hsp90α or combinations of inhibitors of Hsp90α and Bclaf1 to achieve treatment efficacy with lower toxic side effects. Our study also suggests that Bclaf1 expression may represent a suitable biomarker in HCC and perhaps in other cancers.…”

Section: Discussionmentioning

confidence: 98%

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Heat Shock Protein 90α–Dependent B‐Cell‐2–Associated Transcription Factor 1 Promotes Hepatocellular Carcinoma Proliferation by Regulating MYC Proto‐Oncogene c‐MYC mRNA Stability

et al. 2018

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Section: Discussionmentioning

confidence: 98%

“…There is also accumulating evidence that NB interferes with the interaction of Hsp90 with other clients, notably ErbB2, Raf1, and v‐Src, which have been reported to play a critical regulatory role in HCC progression. ( )…”

Section: Discussionmentioning

confidence: 99%

Heat Shock Protein 90α–Dependent B‐Cell‐2–Associated Transcription Factor 1 Promotes Hepatocellular Carcinoma Proliferation by Regulating MYC Proto‐Oncogene c‐MYC mRNA Stability

et al. 2018

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“…Thus, specificity is affected to some extent. Therefore, nucleic acid markers are now largely developed towards based on their biology, such as methylation 35,36 and mutation, [37][38][39] to provide insight into treatment choice or potential drug resistance. As complete cells, CTCs can provide all the same information as nucleic acids.…”

Section: Discussionmentioning

confidence: 99%

<p>Dynamic Changes in Serum Markers and Their Utility in the Early Diagnosis of All Stages of Hepatitis B-Associated Hepatocellular Carcinoma</p>

Wu¹,

Liu²,

Li³

et al. 2020

OTT

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Objective: This study aimed to evaluate the individual and combined diagnostic values of serum alpha-fetoprotein (AFP), des-gamma-carboxyprothrombin (DCP), glypican-3 (GPC3) and golgi protein 73 (GP73) in diagnosing hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Methods: Participants from Beijing YouAn Hospital were enrolled and divided into seven groups. Serum was collected and the levels of AFP, GPC3, GP73 and DCP were simultaneously measured with a protein array. Pearson's χ 2 test was applied to compare the clinicopathological characteristics. Receiver operating characteristic (ROC) curves were used to analyse the diagnostic performance of the four markers. Results: As a single biomarker for differentiating HCC from all controls, AFP had a larger area under the curve (AUC) (0.798, 95% CI (0.754-0.838) than the other biomarkers, with a sensitivity of 77.3% and a specificity of 71.1%. Among the other combinations, AFP plus GPC3 and DCP (0.871, 95% CI (0.833-0.903)) was the best at differentiating HCC from all controls. In discriminating very early stage and early stage HCC from all controls, the AUC of GPC3 (0.744, 95% CI (0.690-0.793); sensitivity 62.8%; specificity 83.3%) was better than that of AFP (0.723, 95% CI (0.668-0.774); sensitivity 67.3%; specificity 71.7%). Among all biomarker combinations, the combination of AFP, GPC3 and GP73 had the largest AUC (0.843, 95% CI (0.796-0.883); sensitivity 84.1%; specificity 71.7%). AFP (AUC 0.726, 95% CI (0.662-0.784)) showed the best performance in the very early diagnosis of HBV-related HCC. Conclusion: As a single biomarker, AFP has an advantage in the very early and early diagnosis of HBV-related HCC. The combination of AFP, GPC3 and GP73 is the most suitable marker for the early diagnosis of HBV-related HCC. However, AFP remains the best biomarker for the very early diagnosis of HBV-related HCC, and the adding of one or more markers does not significantly improve the diagnostic accuracy.

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“…56 Improvement in NGS technology and better understanding of frequent genetic alterations in HCC allowed comprehensive analysis of the mutational landscape of ctDNA and expanded the list of mutation biomarker candidates. [57][58][59] A study of 30 biopsy proven HCC patients were prospectively recruited and deep sequencing of the DNA from the biopsies, cfDNA, and matched germline was performed using a panel targeting 46 coding and noncoding genes frequently altered in HCCs. 57 Two-thirds of the patients had BCLC stage A disease.…”

Section: Mutations In Ctdnamentioning

confidence: 99%

Circulating Tumor DNA and Hepatocellular Carcinoma

2019

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There is a clear and unmet need for biomarkers in hepatocellular carcinoma (HCC). Circulating cell free deoxyribonucleic acid (cfDNA) is a fragmented DNA subtype, found in the blood circulation. Circulating tumor DNA (ctDNA) is the fraction of total cfDNA, which originates from the primary tumor or metastases in patients with cancer. Earlier studies reported that quantitative measurement cfDNA has diagnostic and prognostic role for HCC. More recently, improvement in next-generation sequencing technology and better understanding of genetic or epigenetic alteration of HCC have allowed comprehensive analysis of mutational and methylation landscape of ctDNA. Hotspot mutation panels and methylation panels have both shown promising performance. None of these tests have yet been validated in longitudinal cohorts for preclinical detection of HCC. In this article, the authors discuss the currently available ctDNA detection technologies, their diagnostic and prognostic performance in HCC, and future research directions.

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Next-Generation Sequencing of Circulating Tumor DNA Reveals Frequent Alterations in Advanced Hepatocellular Carcinoma

Cited by 67 publications

References 44 publications

Heat Shock Protein 90α–Dependent B‐Cell‐2–Associated Transcription Factor 1 Promotes Hepatocellular Carcinoma Proliferation by Regulating MYC Proto‐Oncogene c‐MYC mRNA Stability

Heat Shock Protein 90α–Dependent B‐Cell‐2–Associated Transcription Factor 1 Promotes Hepatocellular Carcinoma Proliferation by Regulating MYC Proto‐Oncogene c‐MYC mRNA Stability

<p>Dynamic Changes in Serum Markers and Their Utility in the Early Diagnosis of All Stages of Hepatitis B-Associated Hepatocellular Carcinoma</p>

Circulating Tumor DNA and Hepatocellular Carcinoma

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