Back to Search Start Over

Epigenetic heterogeneity in cancer

Authors :
Mingzhou Guo
Yaojun Peng
Aiai Gao
Chen Du
James G. Herman
Source :
Biomarker Research, Vol 7, Iss 1, Pp 1-19 (2019)
Publication Year :
2019
Publisher :
BMC, 2019.

Abstract

Abstract Phenotypic and functional heterogeneity is one of the hallmarks of human cancers. Tumor genotype variations among tumors within different patients are known as interpatient heterogeneity, and variability among multiple tumors of the same type arising in the same patient is referred to as intra-patient heterogeneity. Subpopulations of cancer cells with distinct phenotypic and molecular features within a tumor are called intratumor heterogeneity (ITH). Since Nowell proposed the clonal evolution of tumor cell populations in 1976, tumor heterogeneity, especially ITH, was actively studied. Research has focused on the genetic basis of cancer, particularly mutational activation of oncogenes or inactivation of tumor-suppressor genes (TSGs). The phenomenon of ITH is commonly explained by Darwinian-like clonal evolution of a single tumor. Despite the monoclonal origin of most cancers, new clones arise during tumor progression due to the continuous acquisition of mutations. It is clear that disruption of the "epigenetic machinery" plays an important role in cancer development. Aberrant epigenetic changes occur more frequently than gene mutations in human cancers. The epigenome is at the intersection of the environment and genome. Epigenetic dysregulation occurs in the earliest stage of cancer. The current trend of epigenetic therapy is to use epigenetic drugs to reverse and/or delay future resistance to cancer therapies. A majority of cancer therapies fail to achieve durable responses, which is often attributed to ITH. Epigenetic therapy may reverse drug resistance in heterogeneous cancer. Complete understanding of genetic and epigenetic heterogeneity may assist in designing combinations of targeted therapies based on molecular information extracted from individual tumors.

Details

Language :
English
ISSN :
20507771
Volume :
7
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Biomarker Research
Publication Type :
Academic Journal
Accession number :
edsdoj.761e0a5819454996828b4c822c5af76c
Document Type :
article
Full Text :
https://doi.org/10.1186/s40364-019-0174-y