@article{70a5611fa0174bf194f5f4607d902c9f,
title = "Mapping extrachromosomal DNA amplifications during cancer progression",
abstract = "To understand the role of extrachromosomal DNA (ecDNA) amplifications in cancer progression, we detected and classified focal amplifications in 8,060 newly diagnosed primary cancers, untreated metastases and heavily pretreated tumors. The ecDNAs were detected at significantly higher frequency in untreated metastatic and pretreated tumors compared to newly diagnosed cancers. Tumors from chemotherapy-pretreated patients showed significantly higher ecDNA frequency compared to untreated cancers. In particular, tubulin inhibition associated with ecDNA increases, suggesting a role for ecDNA in treatment response. In longitudinally matched tumor samples, ecDNAs were more likely to be retained compared to chromosomal amplifications. EcDNAs shared between time points, and ecDNAs in advanced cancers were more likely to harbor localized hypermutation events compared to private ecDNAs and ecDNAs in newly diagnosed tumors. Relatively high variant allele fractions of ecDNA localized hypermutations implicated early ecDNA mutagenesis. Our findings nominate ecDNAs to provide tumors with competitive advantages during cancer progression and metastasis.",
keywords = "Humans, Disease Progression, Neoplasms/genetics, Gene Amplification",
author = "Hoon Kim and Soyeon Kim and Taylor Wade and Eunchae Yeo and Anuja Lipsa and Anna Golebiewska and Johnson, {Kevin C.} and Sepil An and Junyong Ko and Yoonjoo Nam and Lee, {Hwa Yeon} and Seunghyun Kang and Heesuk Chung and Niclou, {Simone P.} and Moon, {Hyo Eun} and Paek, {Sun Ha} and Vineet Bafna and Jens Luebeck and Verhaak, {Roel G.W.}",
note = "Funding This work was delivered as part of the eDyNAmiC team supported by the Cancer Grand Challenges partnership funded by Cancer Research UK (CGCATF-2021/100012; CGCATF-2021/100016 to R.G.W.V.; and CGCATF-2021/100025 to V.B. and J.L.) and the National Cancer Institute (OT2CA278688; OT2CA278649 to R.G.W.V.; and OT2CA278635 to V.B. and J.L.). This work was also supported by the National Institutes of Health (grants R01 CA237208, R21 NS114873 and R33 CA236681 to R.G.W.V.) and Cancer Center Support Grant (P30 CA034196, U24CA264379 and R01GM114362 to V.B.); the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science and ICT; NRF-2019R1A5A2027340 and NRF-2022M3C1A3092022 to H.K.), the Korea Health Industry Development Institute (KHIDI) grant funded by Ministry of Health & Welfare (HI19C1348 to S. Kim) and the Luxembourg National Research Fund (FNR; C20/BM/14646004/GLASSLUX to A.L., A.G. and S.P.N.). Publisher Copyright: {\textcopyright} The Author(s) 2024.",
year = "2024",
month = nov,
doi = "10.1038/s41588-024-01949-7",
language = "English",
volume = "56",
pages = "2447--2454",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Research",
number = "11",
}