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

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.

CAR-T therapy in oncology and other fields of medicine

“…Dodatkowo jest ono komplikowane właśnie przez takie procesy, jak amplifikacja ekstrachromosomalna, ponieważ plastyczność genetyczna komórek wynikająca z tego typu amplifikacji jest znacznie zwiększona [136]. Można obserwować różną liczbę kopii jakiegoś genu w obrębie amplikonów, następnie różną liczbę amplikonów w komórce nowotworowej i co najważniejsze -różne zestawy amplikonów, z różnymi onkogenami w różnych komórkach [137]. Amplikony mogą być wytracane.…”

Untitled

“…These findings apply in particular to the connection of ECC-DNAs in "oncogene amplification" [10], the generation of tumors, [11][12][13][14] their pathogenesis, resp. [15] and acceleration [16]. Certain details revealed on how ECC-DNAs "remodel" genomic DNA [17].…”

Progress on the role of extrachromosomal DNA in tumor pathogenesis and evolution

“…The bridge eventually ruptures, and the broken chromatids inherit unequal amounts of genetic material. The continuous repetition of the whole process of the BFB cycle leads to genome amplification and a variety of chromosomal aberrations, including double‐minute chromosomes 9,47 . Regions amplified by BFB cycles in hamster cells have been proved to form double‐minute chromosomes 48,49 .…”

“…According to the cell and tissue types and genetic background, these DNA molecules show a wide range of heterogeneity in size, which can be classified into two categories: (a) small extrachromosomal circular DNA of hundreds to thousands of bp (base pairs), including telomeric circles, 8‐10 microDNA 9‐11 and small polydispersed circular DNA (spcDNA) 9,10,12 (hereinafter referred to as eccDNA); (b) larger double‐minute chromosomes of several Mb, later referred to as ecDNA that usually contain oncogenes or drug‐resistance genes (Table 1). 9,10,13,14 In this review, we highlight the latest discoveries in this emerging field regarding the role of ecDNA in the context of tumor evolutionary processes. The possible formation mechanisms, structure, and function of ecDNA are also summarized, and the clinical application and future research directions of ecDNA are further discussed in the present review.…”