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 valuable clues for further investigations in understanding the process of tumorigenesis in HCC.
Epigenome-wide association study in hepatocellular carcinoma : Identification of stochastic epigenetic mutations through an innovative statistical approach / D. Gentilini, S. Scala, G. Gaudenzi, P. Garagnani, M. Capri, M. Cescon, G.L. Grazi, M.G. Bacalini, S. Pisoni, A. Dicitore, L. Circelli, S. Santagata, F. Izzo, A.M. Di Blasio, L. Persani, C. Franceschi, G. Vitale. - In: ONCOTARGET. - ISSN 1949-2553. - 8:26(2017 Jun 27), pp. 41890-41902.
|Titolo:||Epigenome-wide association study in hepatocellular carcinoma : Identification of stochastic epigenetic mutations through an innovative statistical approach|
GENTILINI, DAVIDE (Primo)
VITALE, GIOVANNI (Ultimo)
|Parole Chiave:||DNA methylation; epigenetics; genome-wide; hepatocellular carcinoma; stochastic epigenetic mutation|
|Settore Scientifico Disciplinare:||Settore MED/13 - Endocrinologia|
|Progetto:||Piattaforme tecnologiche avanzate per la definizione di nuovi biomarkers e bersagli molecolari in vettori nano tecnologici per la diagnosi e terapia di neoplasie umane|
|Data di pubblicazione:||27-giu-2017|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.18632/oncotarget.17462|
|Appare nelle tipologie:||01 - Articolo su periodico|