SAT-469-Frequency of TP53, CTNNB1, and TERT promoter mutations in patients with hepatocellular carcinoma from Southern Italy

Lombardo, Daniele; Saitta, Carlo; Musolino, Cristina; Navarra, Giuseppe; Raimondo, Giovanni; Pollicino, Teresa

doi:10.1016/s0618-8278(19)31676-7

Cited by 10 publications

(16 citation statements)

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“…Interestingly, the TERT promoter mutation at the −124 bp hotspot appears more often compared with the TERT promoter mutation at the −146 bp hotspot [93,94,[96][97][98]100,101,106,108,111,112,114] was shown that the TERT promoter mutations generate a de novo consensus binding site for the E-twenty-six (ETS) transcription factor family [83,84], leading to an increase in TERT protein amounts, telomerase activity and telomere length [123]. Recently a new TERT promoter mutation was found in 7.5% of the analyzed HCCs at the position −297 (C > T) upstream of the ATG translation start site, which creates an AP2 consensus sequence [104].…”

Section: Tert Promoter Mutationsmentioning

confidence: 99%

“…consensus binding site for the E-twenty-six (ETS) transcription factor family [83,84], leading to an increase in TERT protein amounts, telomerase activity and telomere length [123]. Recently a new TERT promoter mutation was found in 7.5% of the analyzed HCCs at the position −297 (C > T) upstream of the ATG translation start site, which creates an AP2 consensus sequence [104]. Interestingly, the TERT promoter mutation frequency in HCC differs geographically.…”

Section: Tert Promoter Mutationsmentioning

confidence: 99%

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Telomeres and Telomerase in the Development of Liver Cancer

Stroth

Tharehalli

Güneş

et al. 2020

Cancers

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Liver cancer is one of the most common cancer types worldwide and the fourth leading cause of cancer-related death. Liver carcinoma is distinguished by a high heterogeneity in pathogenesis, histopathology and biological behavior. Dysregulated signaling pathways and various gene mutations are frequent in hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), which represent the two most common types of liver tumors. Both tumor types are characterized by telomere shortening and reactivation of telomerase during carcinogenesis. Continuous cell proliferation, e.g., by oncogenic mutations, can cause extensive telomere shortening in the absence of sufficient telomerase activity, leading to dysfunctional telomeres and genome instability by breakage–fusion–bridge cycles, which induce senescence or apoptosis as a tumor suppressor mechanism. Telomerase reactivation is required to stabilize telomere functionality and for tumor cell survival, representing a genetic risk factor for the development of liver cirrhosis and liver carcinoma. Therefore, telomeres and telomerase could be useful targets in hepatocarcinogenesis. Here, we review similarities and differences between HCC and iCCA in telomere biology.

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Section: Tert Promoter Mutationsmentioning

confidence: 99%

Section: Tert Promoter Mutationsmentioning

confidence: 99%

Telomeres and Telomerase in the Development of Liver Cancer

Stroth

Tharehalli

Güneş

et al. 2020

Cancers

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“…Notably, the site of this mutational hotspot is different from that generally found at the codon 249 in exon 7 on p53 in HBV-infected HCC patients who consume food contaminated with AFB 1 [24]. Moreover, the absence of mutations at the codon 249 on the p53 gene of HCC patients has been recently reported in Italy [6], a geographic area where there is no dietary exposure to AFB 1 and where the general prevalence of HBV infection is lower than 1%.…”

Section: Discussionmentioning

confidence: 82%

“…Whole-exome and next generation sequencing data showed that the frequency of p53 mutations is ranging from 28 to 54% in liver tumors from the Cancer Genome Atlas and a Chinese clinical dataset [5]. However, somatic p53 mutations have variable frequencies in different geographic areas, depending on liver disease etiology and environmental parameters [6]. For instance, in Asia and Africa, hepatitis B virus infection and dietary exposure to AFB 1 has been associated with G:C to T:A transversions at the third base in codon 249 of the p53 gene causing R249S substitution.…”

Section: Introductionmentioning

confidence: 99%

Ligation-Mediated Polymerase Chain Reaction Detection of 8-Oxo-7,8-Dihydro-2′-Deoxyguanosine and 5-Hydroxycytosine at the Codon 176 of the p53 Gene of Hepatitis C-Associated Hepatocellular Carcinoma Patients

Galli

Munnia²,

Cellai³

et al. 2020

IJMS

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Molecular mechanisms underlying Hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) pathogenesis are still unclear. Therefore, we analyzed the levels of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and other oxidative lesions at codon 176 of the p53 gene, as well as the generation of 3-(2-deoxy-β-d-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine (M1dG), in a cohort of HCV-related HCC patients from Italy. Detection of 8-oxodG and 5-hydroxycytosine (5-OHC) was performed by ligation mediated-polymerase chain reaction assay, whereas the levels of M1dG were measured by chromatography and mass-spectrometry. Results indicated a significant 130% excess of 8-oxodG at –TGC– position of p53 codon 176 in HCV-HCC cases as compared to controls, after correction for age and gender, whereas a not significant increment of 5-OHC at –TGC– position was found. Then, regression models showed an 87% significant excess of M1dG in HCV-HCC cases relative to controls. Our study provides evidence that increased adduct binding does not occur randomly on the sequence of the p53 gene but at specific sequence context in HCV-HCC patients. By-products of lipid peroxidation could also yield a role in HCV-HCC development. Results emphasize the importance of active oxygen species in inducing nucleotide lesions at a p53 mutational hotspot in HCV-HCC patients living in geographical areas without dietary exposure to aflatoxin B1.

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“…These targets included candidate protein targets (TP53, CCND1, MYC, VEGFA, CTNNB1, RHOA, CCNA2, AR, and HSP90AA1) and human other targets (CDK2, CDH1, CDK1, EP300, and JUN). The mutation of TP53 (cellular tumor antigen p53) and CCND1 (G1/S-specific cyclin-D1), serving as tumor suppressors associated with cell cycle regulation, is regarded as drivers of HCC development [ 49 ]. VEGFA, a growth factor active in angiogenesis and endothelial cell growth, can increase endothelial cell proliferation and reduce the apoptosis of blood vessels.…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology‐Based Study on the Mechanism of Scutellariae Radix for Hepatocellular Carcinoma Treatment

Wang

Liang

Peng

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Hepatocellular carcinoma (HCC) is a malignant tumor without effective therapeutic drugs for most patients in advanced stages. Scutellariae Radix (SR) is a well-known anti-inflammatory and anticarcinogenic herbal medicine. However, the mechanism of SR against HCC remains to be clarified. In the present study, network pharmacology was utilized to characterize the mechanism of SR on HCC. The active components of SR and their targets were collected from the traditional Chinese medicine systems pharmacology database and the traditional Chinese medicine integrated database. HCC-related targets were acquired from the liver cancer databases OncoDB.HCC and Liverome. The gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathway were analyzed using the Database for Annotation, Visualization, and Integrated Discovery. Component-component target and protein-protein interaction networks were set up. A total of 143 components of SR were identified, and 37 of them were considered as candidate active components. Fifty targets corresponding to 29 components of SR were mapped with targets of HCC. Functional enrichment analysis indicated that SR exerted an antihepatocarcinoma effect by regulating pathways in cancer, hepatitis B, viral carcinogenesis, and PI3K-Akt signaling. The holistic approach of network pharmacology can provide novel insights into the mechanistic study and therapeutic drug development of SR for HCC treatment.

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SAT-469-Frequency of TP53, CTNNB1, and TERT promoter mutations in patients with hepatocellular carcinoma from Southern Italy

Cited by 10 publications

References 0 publications

Telomeres and Telomerase in the Development of Liver Cancer

Telomeres and Telomerase in the Development of Liver Cancer

Ligation-Mediated Polymerase Chain Reaction Detection of 8-Oxo-7,8-Dihydro-2′-Deoxyguanosine and 5-Hydroxycytosine at the Codon 176 of the p53 Gene of Hepatitis C-Associated Hepatocellular Carcinoma Patients

Network Pharmacology‐Based Study on the Mechanism of Scutellariae Radix for Hepatocellular Carcinoma Treatment

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