Epigenome-wide association study in hepatocellular carcinoma: Identification of stochastic epigenetic mutations through an innovative statistical approach

Oncotarget
Davide GentiliniGiovanni Vitale

Abstract

Hepatocellular carcinoma (HCC) results from accumulation of both genetic and epigenetic alterations. We investigated the genome-wide DNA methylation profile in 69 pairs of HCC and adjacent non-cancerous liver tissues using the Infinium HumanMethylation 450K BeadChip array. An innovative analytical approach has been adopted to identify Stochastic Epigenetic Mutations (SEMs) in HCC.HCC and peritumoral tissues showed a different epigenetic profile, mainly characterized by loss of DNA methylation in HCC. Total number of SEMs was significantly higher in HCC tumor (median: 77,370) than in peritumoral (median: 5,656) tissues and correlated with tumor grade. A significant positive association emerged between SEMs measured in peritumoral tissue and hepatitis B and/or C virus infection status. A restricted number of SEMs resulted to be shared by more than 90% of HCC tumor samples and never present in peritumoral tissue. This analysis allowed the identification of four epigenetically regulated candidate genes (AJAP1, ADARB2, PTPRN2, SDK1), potentially involved in the pathogenesis of HCC.In conclusion, HCC showed a methylation profile completely deregulated and very far from adjacent non-cancerous liver tissues. The SEM analysis provided v...Continue Reading

References

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Citations

Mar 16, 2018·International Journal of Cancer. Journal International Du Cancer·Antonio FaddaPatrizia Zavattari
Sep 20, 2017·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Eduardo Fernandez-RebolloWolfgang Wagner
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Jul 28, 2020·International Journal of Molecular Sciences·Elena SpadaDavide Gentilini
Sep 24, 2020·International Journal of Molecular Sciences·Nina Milutin GašperovMagdalena Grce
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Jul 28, 2021·Epigenetics : Official Journal of the DNA Methylation Society·Andrea G IzquierdoAna B Crujeiras

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Methods Mentioned

BETA
transfection
surgical resection
chip
biopsies

Software Mentioned

R car package
R outliers package
RnBeads
methylumi
minfi
limma
R package “ FactoMineR ”
R package stats
Phenolyzer
R

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