Mutations in circulating tumor DNA predict primary resistance to systemic therapies in advanced hepatocellular carcinoma

Felden, Johann von; Craig, Amanda; García‐Lezana, Teresa; Labgaa, Ismaïl; Haber, Philipp K.; D’Avola, Delia; Asgharpour, Amon; Dieterich, Douglas T.; Bonaccorso, Antoinette; Torres‐Martín, Miguel; Sia, Daniela; Sung, Max W.; Tabrizian, Parissa; Schwartz, Myron; Llovet, Josep M.; Villanueva, Augusto

doi:10.1038/s41388-020-01519-1

Cited by 96 publications

(93 citation statements)

References 41 publications

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“…The difference between our study and previous studies may be attributed to the different hepatitis backgrounds. In previous studies, HCV infection was the most common in enrolled patients [11][12][13][14]. While in our study, all patients were HBsAg positive and without HCV infection.…”

Section: Discussionmentioning

confidence: 43%

“…TERT has been reported to be the most common mutated gene in HCC patients, with the frequency ranged from 51-60% [11][12][13][14]. In this study, the mutation frequency of TERT was 42.0%, which was lower than TP53 (56.8%).…”

Section: Discussionmentioning

confidence: 52%

“…Key genes mutated in HCC tissues were identi ed by Next-generation sequencing (NGS). The most common mutated genes included telomerase reverse transcriptase (TERT), TP53 and CTNNB1 [11][12][13][14]. As a catalytic component of telomerase complex, TERT could active the telomerase, thereby causing the telomere lengths maintained and cell survival [15].…”

Section: Introductionmentioning

confidence: 99%

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TERT Mutations Correlated With the Prognosis of Patients With Hepatitis B-Related Hepatocellular Carcinoma Underwent Curative Hepatectomy

Song¹,

Huo²,

He³

et al. 2021

Preprint

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Background To explore the value of TERT mutations in predicting the early recurrence and prognosis of hepatitis B-related hepatocellular carcinoma (HCC) patients underwent curative hepatectomy.Methods A total of 81 patients with hepatitis B-related HCC were enrolled and all patients underwent curative hepatectomy. Associations were sought between TERT mutations and recurrence rate within 2 years after hepatectomy, time to progress (TTP) and overall survival (OS).Results TERT mutations (HR: 2.985, 95%CI: 1.158-7.692, p=0.024) and Barcelona clinic liver (BCLC) stage B (HR: 3.326, 95%CI: 1.019-10.856, p=0.046) were independent risk factors for recurrence within 2 years after hepatectomy. Patients with a TERT mutation had poor TTP (p=0.003) and OS (p=0.013) than others. TERT mutations (HR: 2.245, 95%CI: 1.185-4.252, p=0.013) and BCLC stage B (HR: 2.132, 95%CI: 1.082-4.198, p=0.029) were independent risk factors for poor TTP after curative hepatectomy. A predictive model based on TERT mutations and BCLC stage had better ability to predict early recurrence after hepatectomy of HCC patients than any single factor (AUC: 0.688 vs. 0.639, 0.688 vs. 0.607, respectively). Patients with both TERT mutations and BCLC stage B had poorer TTP and OS than others (p=0.001, p<0.001, respectively).Conclusion TERT mutations had ability to predict early recurrence and poor prognosis for hepatitis B-related HCC patients underwent curative hepatectomy.

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Section: Discussionmentioning

confidence: 43%

Section: Discussionmentioning

confidence: 52%

Section: Introductionmentioning

confidence: 99%

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TERT Mutations Correlated With the Prognosis of Patients With Hepatitis B-Related Hepatocellular Carcinoma Underwent Curative Hepatectomy

Song¹,

Huo²,

He³

et al. 2021

Preprint

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“…Targeted ultra-deep sequencing of 25 genes and Digital Droplet PCR of the TERT promoter in ctDNA have been exploited to identify predictors of primary resistance of advanced-staged HCC patients to systemic therapies. The most frequent mutations in the ctDNA of patients with advanced HCC were TERT promoter (51%), TP53 (32%), CTNNB1 (17%), PTEN (8%), AXIN1, ARID2, KMT2D, and TSC2 (6% each) (49). TP53 and CTNNB1 mutations were mutually exclusive.…”

Section: Genomic Signatures Of Circulating Tumor Dnamentioning

confidence: 99%

Genomic Landscape of Liquid Biopsy for Hepatocellular Carcinoma Personalized Medicine

Moldogazieva

Zavadskiy

Terentiev

2021

Cancer Genomics Proteomics

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Hepatocellular carcinoma (HCC) is the sixth most frequently diagnosed cancer and the third leading cause of cancer-related deaths worldwide. Advanced-stage HCC patients have poor survival rates and this requires the discovery of novel clear biomarkers for HCC early diagnosis and prognosis, identifying risk factors, distinguishing HCC from non-HCC liver diseases, and assessment of treatment response. Liquid biopsy has emerged as a novel minimally invasive approach to enable monitoring tumor progression, metastasis, and recurrence. Since the liquid biopsy analysis has relatively high specificity and low sensitivity in cancer early detection, there is a risk of bias. Next-generation sequencing (NGS) technologies provide accurate and comprehensive gene expression and mutational profiling of liquid biopsies including cell-free circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and genomic components of extracellular vesicles (EVs) including micro-RNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). Since HCC is a highly heterogeneous cancer, HCC patients can display various genomic, epigenomic, and transcriptomic patterns and exhibit varying sensitivity to treatment options. Identification 369 This article is freely accessible online.

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“…Targeted-sequencing of various panels of genes further confirmed the prognostic impact of ctDNA detection, associated with worse survival or higher recurrence [ 30 ]. Providing more detailed analyses than just the simple presence/absence of ctDNA, Kim et al showed that MLH1 mutation was specifically associated with lower survival [ 35 ], whereas von Felden et al recently demonstrated that mutations of genes from the PI3K/mTOR pathway were predictors of non-response to tyrosine kinase inhibitors (TKI) in patients with advanced HCC [ 38 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of Liquid Biopsy in Hepatocellular Carcinoma Prognostication

Labgaa

Villanueva

Dormond

et al. 2021

Cancers

Self Cite

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Showing a steadily increasing cancer-related mortality, the epidemiological evolution of hepatocellular carcinoma (HCC) is concerning. Numerous strategies have attempted to prognosticate HCC but their performance is modest; this is partially due to the heterogeneous biology of this cancer. Current clinical guidelines endorse classifications and scores that use clinical variables, such as the Barcelona Clinic Liver Cancer (BCLC) classification. These algorithms are unlikely to fully recapitulate the genomic complexity of HCC. Integrating molecular readouts on a patient-basis, following a precision-medicine perspective, might be an option to refine prognostic systems. The limited access to HCC tissue samples is an important limitation to these approaches but it could be partially circumvented by using liquid biopsy. This concept consists of the molecular analysis of products derived from a solid tumor and released into biological fluids, mostly into the bloodstream. It offers an easy and minimally-invasive access to DNA, RNA, extracellular vesicles and cells that can be analyzed with next-generation sequencing (NGS) technologies. This review aims to investigate the potential contributions of liquid biopsy in HCC prognostication. The results identified prognostic values for each of the components of liquid biopsy, suggesting that this technology may help refine HCC prognostication.

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Mutations in circulating tumor DNA predict primary resistance to systemic therapies in advanced hepatocellular carcinoma

Cited by 96 publications

References 41 publications

TERT Mutations Correlated With the Prognosis of Patients With Hepatitis B-Related Hepatocellular Carcinoma Underwent Curative Hepatectomy

TERT Mutations Correlated With the Prognosis of Patients With Hepatitis B-Related Hepatocellular Carcinoma Underwent Curative Hepatectomy

Genomic Landscape of Liquid Biopsy for Hepatocellular Carcinoma Personalized Medicine

The Role of Liquid Biopsy in Hepatocellular Carcinoma Prognostication

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