Studying the frequency of aberrant DNA methylation of APC, P14, and E-cadherin genes in HCV-related hepatocarcinogenesis

Mekky, Mohamed A.; Salama, Rgaa H; Abdelaal, Mahmoud; Ghaliony, Mohamed A. A.; Zaky, Saad

doi:10.3233/cbm-171156

Cited by 8 publications

(7 citation statements)

References 29 publications

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“…Differential methylation was observed at CpGs associated with P14 and RASSF1A , previously shown to be aberrantly methylated in HCC (Fig. B) [51–53]. In the CLD samples, we detected 586 DM CpGs compared with normal liver (Fig.…”

Section: Resultsmentioning

confidence: 57%

Epigenetic priming in chronic liver disease impacts the transcriptional and genetic landscapes of hepatocellular carcinoma

et al. 2021

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Hepatocellular carcinomas (HCCs) usually arise from chronic liver disease (CLD). Precancerous cells in chronically inflamed environments may be ‘epigenetically primed’, sensitising them to oncogenic transformation. We investigated whether epigenetic priming in CLD may affect HCC outcomes by influencing the genomic and transcriptomic landscapes of HCC. Analysis of DNA methylation arrays from 10 paired CLD‐HCC identified 339 shared dysregulated CpG sites and 18 shared differentially methylated regions compared with healthy livers. These regions were associated with dysregulated expression of genes with relevance in HCC, including ubiquitin D (UBD), cytochrome P450 family 2 subfamily C member 19 (CYP2C19) and O‐6‐methylguanine‐DNA methyltransferase (MGMT). Methylation changes were recapitulated in an independent cohort of nine paired CLD‐HCC. High CLD methylation score, defined using the 124 dysregulated CpGs in CLD and HCC in both cohorts, was associated with poor survival, increased somatic genetic alterations and TP53 mutations in two independent HCC cohorts. Oncogenic transcriptional and methylation dysregulation is evident in CLD and compounded in HCC. Epigenetic priming in CLD sculpts the transcriptional landscape of HCC and creates an environment favouring the acquisition of genetic alterations, suggesting that the extent of epigenetic priming in CLD could influence disease outcome.

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Section: Resultsmentioning

confidence: 57%

Epigenetic priming in chronic liver disease impacts the transcriptional and genetic landscapes of hepatocellular carcinoma

et al. 2021

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“…60 For example, HCV induces epigenetic modifications that can result in genome instability due to global hypomethylation, releasing suppression of oncogenes such as HRAS, KRAS and NRAS, as well as silencing of tumour suppressor genes such as APC, P14 and E-cadherin via hypermethylation. 59,61 Therefore, delayed treatment of known HCV infection represents a worst-case cost scenario, in which the high costs of DAA therapy do not offset the potentially much higher costs of treatment for cirrhosis or HCC. It is not necessary just to treat HCV infection; it is necessary to do so promptly.…”

Section: Long -Term Cos Ts and Ris K Smentioning

confidence: 99%

“…The proliferative pathways and epigenetic changes induced during long‐term HCV infection are not necessarily restored to the pre‐HCV state even when the virus is eliminated, indicating that some effects of HCV infection are irreversible 60 . For example, HCV induces epigenetic modifications that can result in genome instability due to global hypomethylation, releasing suppression of oncogenes such as HRAS, KRAS and NRAS, as well as silencing of tumour suppressor genes such as APC, P14 and E‐cadherin via hypermethylation 59,61 . Therefore, delayed treatment of known HCV infection represents a worst‐case cost scenario, in which the high costs of DAA therapy do not offset the potentially much higher costs of treatment for cirrhosis or HCC.…”

Section: Long‐term Costs and Risksmentioning

confidence: 99%

Road to elimination of HCV: Clinical challenges in HCV management

Hayes

Imamura

Tanaka

et al. 2022

Liver International

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In 2020, the Nobel Prize in Medicine was award to Harvey J. Alter, Michael Houghton and Charles M. Rice for their work on the discovery of hepatitis C virus (HCV). The race to identify and screen the 'non-A, non-B' virus contaminating the blood supply was a transformative technical breakthrough that resulted in not only a safer blood supply but also in major advances in virology, immunology, diagnostic testing and liver pathology. 1 At the National Institutes of Health, Harvey J. Alter showed that hepatitis cases associated with

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“…Several studies have shown that DNA hypermethylation in cancer cells targets tumor suppressor genes explicitly, resulting in growth selection and uncontrolled cell proliferation [25,26,27,28]. Many tumor suppressor genes are inactivated by this mechanism in cancer such as the adenomatous polyposis coli (APC) [29], retinoblastoma (Rb) [30], Von Hippel-Lindau (VHL), BRCA1 [31], and several other genes that are involved in DNA repair (MGMT; O-6-Methylguanine-DNA Methyltransferase), cell cycle progression (p16 INK4a , p15 INK4b ), apoptosis (DAPK; death-associated protein kinase-1), or antioxidation (GSTP1; Glutathione S-Transferase P-1) [32]. The extent to which DNA de novo methylation contributes to cancer development and progression varies among different types of cancer; very high in colon cancer, while rare in brain tumors [33].…”

Section: Dna Methylation In Cancermentioning

confidence: 99%

Methyl Donor Micronutrients that Modify DNA Methylation and Cancer Outcome

2019

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DNA methylation is an epigenetic mechanism that is essential for regulating gene transcription. However, aberrant DNA methylation, which is a nearly universal finding in cancer, can result in disturbed gene expression. DNA methylation is modified by environmental factors such as diet that may modify cancer risk and tumor behavior. Abnormal DNA methylation has been observed in several cancers such as colon, stomach, cervical, prostate, and breast cancers. These alterations in DNA methylation may play a critical role in cancer development and progression. Dietary nutrient intake and bioactive food components are essential environmental factors that may influence DNA methylation either by directly inhibiting enzymes that catalyze DNA methylation or by changing the availability of substrates required for those enzymatic reactions such as the availability and utilization of methyl groups. In this review, we focused on nutrients that act as methyl donors or methylation co-factors and presented intriguing evidence for the role of these bioactive food components in altering DNA methylation patterns in cancer. Such a role is likely to have a mechanistic impact on the process of carcinogenesis and offer possible therapeutic potentials.

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Studying the frequency of aberrant DNA methylation of APC, P14, and E-cadherin genes in HCV-related hepatocarcinogenesis

Abstract: Aberrant DNA methylation of multiple genes is associated with disease progression in HCV related cirrhosis. Moreover, early detection of promotor methylation of these may sever as good biomarker for early detection and therapeutic targets in high risk patients.

Cited by 8 publications

References 29 publications

Epigenetic priming in chronic liver disease impacts the transcriptional and genetic landscapes of hepatocellular carcinoma

Epigenetic priming in chronic liver disease impacts the transcriptional and genetic landscapes of hepatocellular carcinoma

Road to elimination of HCV: Clinical challenges in HCV management

Methyl Donor Micronutrients that Modify DNA Methylation and Cancer Outcome

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