Current understanding of extrachromosomal circular DNA in cancer pathogenesis and therapeutic resistance

Yuanliang Yan,Zhicheng Gong,Ming Gao,Zhijie Xu,Jinzhou Huang,Guijie Guo,Shuangshuang Zeng,Qian Zhu

doi:10.1186/s13045-020-00960-9

Abstract

Extrachromosomal circular DNA was recently found to be particularly abundant in multiple human cancer cells, although its frequency varies among different tumor types. Elevated levels of extrachromosomal circular DNA have been considered an effective biomarker of cancer pathogenesis. Multiple reports have demonstrated that the amplification of oncogenes and therapeutic resistance genes located on extrachromosomal DNA is a frequent event that drives intratumoral genetic heterogeneity and provides a potential evolutionary advantage. This review highlights the current understanding of the extrachromosomal circular DNA present in the tissues and circulation of patients with advanced cancers and provides a detailed discussion of their substantial roles in tumor regulation. Confirming the presence of cancer-related extrachromosomal circular DNA would provide a putative testing strategy for the precision diagnosis and treatment of human malignancies in clinical practice.

Highlights

Extrachromosomal circular DNA, first described by Hotta’s group in 1964, is highly conserved across multiple species [1]
The oncogenes amplified in circular DNA structures were shown to lead to high levels of mRNA transcripts, such as epidermal growth factor receptor (EGFR), mouse double minute 2 (MDM2), and cyclin D1 (CCND1) [11, 16]
We focused exclusively on extrachromosomal circular DNA and its substantial tumor-regulating roles in cancer pathogenesis (Fig. 2)

Summary

Introduction

Extrachromosomal circular DNA, first described by Hotta’s group in 1964, is highly conserved across multiple species [1]. If DMs can be explored and characterized accurately with cytogenetic methods [111], it might help the researcher evaluate the effectiveness of anticancer drugs on the subclones of cancer cells that contain DMs. Extrachromosomal circular DNA-based oncogene overexpression The chimeric circularization and amplification of circular DNA is very common and typically has a profound impact on the enhanced expression of oncogenes. The classical MTX resistance gene DHFR was proven to amplify primarily in the form of DMs, contributing to tumor progression and the development of MTX resistance in human colon cancer cells.

Results

Conclusion