Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Clinical Significance of Epigenetic Alterations in Human Hepatocellular Carcinoma and Its Association with Genetic Mutations

Clinical Significance of Epigenetic Alterations in Human Hepatocellular Carcinoma and Its... Accumulation of genetic and epigenetic alterations is a hallmark of cancer genomes, including those in hepatocellular carcinoma (HCC). Particularly, in human HCC, epigenetic changes are more frequently observed than genetic changes in a variety of cancer-related genes, suggesting a potential role for epigenetic alterations during hepatocarcinogenesis. Several environmental factors, such as inflammation, obesity, and steatosis, are reported to affect the epigenetic status in hepatocytes, which could play a role in HCC development. In addition, genetic mutations in histone modulators and chromatin regulators would be critical for the acceleration of epigenetic alteration. It is also possible that major genetic mutations of HCC, such as TP53 and CNTTB1 mutations, are associated with the disturbance of epigenetic integrity. For example, specific TP53 mutations frequently induced by aflatoxin B1 exposure might affect histone modifiers and nucleosome remodelers. Generally, epigenetic alteration is reversible, because of which dysregulation of transcription takes place, without affecting protein structure. Therefore, differentiation therapy is one of the potential approaches for HCC with advanced epigenetic alterations. On the other hand, a tumor carrying an accumulation of genetic mutations would result in many abnormal proteins that could be recognized as non-self and could be targets for immune reactions; thus, immune-checkpoint blockers should be effective for HCCs with genetic hypermutation. Although the emergence of genetic and epigenetic alterations could be linked to each other and there could be some crossover or convergence between these cancer pathways, characterization of the mutation spectrum of genetic and epigenetic alterations could influence future HCC treatment. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Digestive Diseases Karger

Clinical Significance of Epigenetic Alterations in Human Hepatocellular Carcinoma and Its Association with Genetic Mutations

Nishida, Naoshi; Kudo, Masatoshi
Digestive Diseases , Volume 34 (6): 6 – Jan 1, 2016
Download PDF
6 pages

Loading next page...
 
/lp/karger/clinical-significance-of-epigenetic-alterations-in-human-blpt897WkA

References (41)

Publisher
Karger
Copyright
© 2016 S. Karger AG, Basel
ISSN
0257-2753
eISSN
1421-9875
DOI
10.1159/000448863
Publisher site
See Article on Publisher Site

Abstract

Accumulation of genetic and epigenetic alterations is a hallmark of cancer genomes, including those in hepatocellular carcinoma (HCC). Particularly, in human HCC, epigenetic changes are more frequently observed than genetic changes in a variety of cancer-related genes, suggesting a potential role for epigenetic alterations during hepatocarcinogenesis. Several environmental factors, such as inflammation, obesity, and steatosis, are reported to affect the epigenetic status in hepatocytes, which could play a role in HCC development. In addition, genetic mutations in histone modulators and chromatin regulators would be critical for the acceleration of epigenetic alteration. It is also possible that major genetic mutations of HCC, such as TP53 and CNTTB1 mutations, are associated with the disturbance of epigenetic integrity. For example, specific TP53 mutations frequently induced by aflatoxin B1 exposure might affect histone modifiers and nucleosome remodelers. Generally, epigenetic alteration is reversible, because of which dysregulation of transcription takes place, without affecting protein structure. Therefore, differentiation therapy is one of the potential approaches for HCC with advanced epigenetic alterations. On the other hand, a tumor carrying an accumulation of genetic mutations would result in many abnormal proteins that could be recognized as non-self and could be targets for immune reactions; thus, immune-checkpoint blockers should be effective for HCCs with genetic hypermutation. Although the emergence of genetic and epigenetic alterations could be linked to each other and there could be some crossover or convergence between these cancer pathways, characterization of the mutation spectrum of genetic and epigenetic alterations could influence future HCC treatment.

Journal

Digestive Diseases – Karger

Published: Jan 1, 2016

Keywords: Chromatin; Mutation; DNA methylation; Histone; Hepatocellular carcinoma

There are no references for this article.