TY - JOUR
T1 - Extrachromosomal DNA (ecDNA) in cancer pathogenesis
AU - Wu, Sihan
AU - Bafna, Vineet
AU - Mischel, Paul S.
N1 - Funding Information:
This work was supported by the Ludwig Institute for Cancer Research (P.S.M.), Defeat GBM Program of the National Brain Tumor Society (P.S.M.), NVIDIA Foundation, Compute for the Cure (P.S.M.), Ben and Catherine Ivy Foundation (P.S.M.).
Publisher Copyright:
© 2021
PY - 2021/2
Y1 - 2021/2
N2 - In cancer, oncogenes and surrounding regulatory regions can untether themselves from chromosomes, forming extrachromosomal DNA particles (ecDNAs). Because of their non-chromosomal inheritance, ecDNA drives high oncogene copy number and intratumoral genetic heterogeneity, endowing tumors with the ability to rapidly change their genomes, accelerating tumor evolution, and contributing to therapeutic resistance. Further, the circular topology of ecDNA leads to enhanced chromatin accessibility, altered gene regulation, and massive oncogene transcription, driving tumor growth and progression, and placing ecDNA at the interface of cancer genomics and epigenetics. Recent studies show that ecDNA is a common event in many of the most aggressive forms of cancer, potentially challenging our current precision oncology approaches. In this review, we discuss what is known about ecDNA and its biological and clinical impact, highlighting new research and suggesting the promise, and some of the challenges ahead for the field.
AB - In cancer, oncogenes and surrounding regulatory regions can untether themselves from chromosomes, forming extrachromosomal DNA particles (ecDNAs). Because of their non-chromosomal inheritance, ecDNA drives high oncogene copy number and intratumoral genetic heterogeneity, endowing tumors with the ability to rapidly change their genomes, accelerating tumor evolution, and contributing to therapeutic resistance. Further, the circular topology of ecDNA leads to enhanced chromatin accessibility, altered gene regulation, and massive oncogene transcription, driving tumor growth and progression, and placing ecDNA at the interface of cancer genomics and epigenetics. Recent studies show that ecDNA is a common event in many of the most aggressive forms of cancer, potentially challenging our current precision oncology approaches. In this review, we discuss what is known about ecDNA and its biological and clinical impact, highlighting new research and suggesting the promise, and some of the challenges ahead for the field.
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U2 - 10.1016/j.gde.2021.01.001
DO - 10.1016/j.gde.2021.01.001
M3 - Review article
C2 - 33477016
AN - SCOPUS:85099589331
SN - 0959-437X
VL - 66
SP - 78
EP - 82
JO - Current Opinion in Genetics and Development
JF - Current Opinion in Genetics and Development
ER -