TY - JOUR
T1 - Extrachromosomal DNA
T2 - An Emerging Hallmark in Human Cancer
AU - Wu, Sihan
AU - Bafna, Vineet
AU - Chang, Howard Y.
AU - Mischel, Paul S.
N1 - Funding Information:
S.W. is a scholar of and is supported by the Cancer Prevention and Research Institute of Texas (RR210034). H.Y.C. is an investigator of the Howard Hughes Medical Institute and supported by R35-CA209919. V.B. is supported by U24CA264379 and R01GM114362. P.S.M. is supported by RO1-CA238249.
Funding Information:
S.W. is a scholar of and is supported by the Cancer Prevention and Research Institute of Texas (RR210034).H.Y.C. is an investigator of the Howard HughesMedical Institute and supported by R35-CA209919. V.B. is supported by U24CA264379 and R01GM114362. P.S.M. is supported by RO1-CA238249.
Publisher Copyright:
Copyright © 2022 by Annual Reviews. All rights reserved.
PY - 2021
Y1 - 2021
N2 - Human genes are arranged on 23 pairs of chromosomes, but in cancer, tumor-promoting genes and regulatory elements can free themselves from chromosomes and relocate to circular, extrachromosomal pieces of DNA (ecDNA). ecDNA, because of its nonchromosomal inheritance, drives high-copy-number oncogene amplification and enables tumors to evolve their genomes rapidly. Furthermore, the circular ecDNA architecture fundamentally alters gene regulation and transcription, and the higher-order organization of ecDNA contributes to tumor pathogenesis. Consequently, patients whose cancers harbor ecDNA have significantly shorter survival. Although ecDNA was first observed more than 50 years ago, its critical importance has only recently come to light. In this review, we discuss the current state of understanding of how ecDNAs form and function as well as how they contribute to drug resistance and accelerated cancer evolution.
AB - Human genes are arranged on 23 pairs of chromosomes, but in cancer, tumor-promoting genes and regulatory elements can free themselves from chromosomes and relocate to circular, extrachromosomal pieces of DNA (ecDNA). ecDNA, because of its nonchromosomal inheritance, drives high-copy-number oncogene amplification and enables tumors to evolve their genomes rapidly. Furthermore, the circular ecDNA architecture fundamentally alters gene regulation and transcription, and the higher-order organization of ecDNA contributes to tumor pathogenesis. Consequently, patients whose cancers harbor ecDNA have significantly shorter survival. Although ecDNA was first observed more than 50 years ago, its critical importance has only recently come to light. In this review, we discuss the current state of understanding of how ecDNAs form and function as well as how they contribute to drug resistance and accelerated cancer evolution.
KW - cancer genomics
KW - ecDNA
KW - extrachromosomal DNA
KW - gene amplification
KW - non-Mendelian inheritance
KW - tumor evolution
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U2 - 10.1146/annurev-pathmechdis-051821-114223
DO - 10.1146/annurev-pathmechdis-051821-114223
M3 - Review article
C2 - 34752712
AN - SCOPUS:85123879057
SN - 1553-4006
VL - 17
SP - 367
EP - 386
JO - Annual Review of Pathology: Mechanisms of Disease
JF - Annual Review of Pathology: Mechanisms of Disease
ER -