Extrachromosomal DNA is associated with oncogene amplification and poor outcome across multiple cancers. Kim, H., Nguyen, N. P., Turner, K., Wu, S., Gujar, A. D., Luebeck, J., Liu, J., Deshpande, V., Rajkumar, U., Namburi, S., Amin, S. B., Yi, E., Menghi, F., Schulte, J. H., Henssen, A. G., Chang, H. Y., Beck, C. R., Mischel, P. S., Bafna, V., & Verhaak, R. G. W. Nat Genet, 52(9):891-897, 2020. 1546-1718 Kim, Hoon Orcid: 0000-0003-4244-6126 Nguyen, Nam-Phuong Turner, Kristen Wu, Sihan Orcid: 0000-0001-8329-7492 Gujar, Amit D Orcid: 0000-0003-0689-6680 Luebeck, Jens Orcid: 0000-0003-4391-979x Liu, Jihe Orcid: 0000-0002-6111-1498 Deshpande, Viraj Rajkumar, Utkrisht Namburi, Sandeep Amin, Samirkumar B Yi, Eunhee Orcid: 0000-0002-7839-7795 Menghi, Francesca Schulte, Johannes H Henssen, Anton G Orcid: 0000-0003-1534-778x Chang, Howard Y Orcid: 0000-0002-9459-4393 Beck, Christine R Orcid: 0000-0001-7821-8489 Mischel, Paul S Orcid: 0000-0002-4560-2211 Bafna, Vineet Orcid: 0000-0002-5810-6241 Verhaak, Roel G W Orcid: 0000-0003-2773-0436 RM1 HG007735/HG/NHGRI NIH HHS/United States R01 CA190121/CA/NCI NIH HHS/United States R21 NS114873/NS/NINDS NIH HHS/United States R35 GM133600/GM/NIGMS NIH HHS/United States R01 NS073831/NS/NINDS NIH HHS/United States P50 HG007735/HG/NHGRI NIH HHS/United States R01 CA237208/CA/NCI NIH HHS/United States P30 CA023100/CA/NCI NIH HHS/United States R01 GM114362/GM/NIGMS NIH HHS/United States R35 CA209919/CA/NCI NIH HHS/United States HHMI/Howard Hughes Medical Institute/United States P30 CA034196/CA/NCI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. United States 2020/08/19 Nat Genet. 2020 Sep;52(9):891-897. doi: 10.1038/s41588-020-0678-2. Epub 2020 Aug 17.doi abstract bibtex Extrachromosomal DNA (ecDNA) amplification promotes intratumoral genetic heterogeneity and accelerated tumor evolution(1-3); however, its frequency and clinical impact are unclear. Using computational analysis of whole-genome sequencing data from 3,212 cancer patients, we show that ecDNA amplification frequently occurs in most cancer types but not in blood or normal tissue. Oncogenes were highly enriched on amplified ecDNA, and the most common recurrent oncogene amplifications arose on ecDNA. EcDNA amplifications resulted in higher levels of oncogene transcription compared to copy number-matched linear DNA, coupled with enhanced chromatin accessibility, and more frequently resulted in transcript fusions. Patients whose cancers carried ecDNA had significantly shorter survival, even when controlled for tissue type, than patients whose cancers were not driven by ecDNA-based oncogene amplification. The results presented here demonstrate that ecDNA-based oncogene amplification is common in cancer, is different from chromosomal amplification and drives poor outcome for patients across many cancer types.
@article{RN6074,
author = {Kim, H. and Nguyen, N. P. and Turner, K. and Wu, S. and Gujar, A. D. and Luebeck, J. and Liu, J. and Deshpande, V. and Rajkumar, U. and Namburi, S. and Amin, S. B. and Yi, E. and Menghi, F. and Schulte, J. H. and Henssen, A. G. and Chang, H. Y. and Beck, C. R. and Mischel, P. S. and Bafna, V. and Verhaak, R. G. W.},
title = {Extrachromosomal DNA is associated with oncogene amplification and poor outcome across multiple cancers},
journal = {Nat Genet},
volume = {52},
number = {9},
pages = {891-897},
note = {1546-1718
Kim, Hoon
Orcid: 0000-0003-4244-6126
Nguyen, Nam-Phuong
Turner, Kristen
Wu, Sihan
Orcid: 0000-0001-8329-7492
Gujar, Amit D
Orcid: 0000-0003-0689-6680
Luebeck, Jens
Orcid: 0000-0003-4391-979x
Liu, Jihe
Orcid: 0000-0002-6111-1498
Deshpande, Viraj
Rajkumar, Utkrisht
Namburi, Sandeep
Amin, Samirkumar B
Yi, Eunhee
Orcid: 0000-0002-7839-7795
Menghi, Francesca
Schulte, Johannes H
Henssen, Anton G
Orcid: 0000-0003-1534-778x
Chang, Howard Y
Orcid: 0000-0002-9459-4393
Beck, Christine R
Orcid: 0000-0001-7821-8489
Mischel, Paul S
Orcid: 0000-0002-4560-2211
Bafna, Vineet
Orcid: 0000-0002-5810-6241
Verhaak, Roel G W
Orcid: 0000-0003-2773-0436
RM1 HG007735/HG/NHGRI NIH HHS/United States
R01 CA190121/CA/NCI NIH HHS/United States
R21 NS114873/NS/NINDS NIH HHS/United States
R35 GM133600/GM/NIGMS NIH HHS/United States
R01 NS073831/NS/NINDS NIH HHS/United States
P50 HG007735/HG/NHGRI NIH HHS/United States
R01 CA237208/CA/NCI NIH HHS/United States
P30 CA023100/CA/NCI NIH HHS/United States
R01 GM114362/GM/NIGMS NIH HHS/United States
R35 CA209919/CA/NCI NIH HHS/United States
HHMI/Howard Hughes Medical Institute/United States
P30 CA034196/CA/NCI NIH HHS/United States
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
United States
2020/08/19
Nat Genet. 2020 Sep;52(9):891-897. doi: 10.1038/s41588-020-0678-2. Epub 2020 Aug 17.},
abstract = {Extrachromosomal DNA (ecDNA) amplification promotes intratumoral genetic heterogeneity and accelerated tumor evolution(1-3); however, its frequency and clinical impact are unclear. Using computational analysis of whole-genome sequencing data from 3,212 cancer patients, we show that ecDNA amplification frequently occurs in most cancer types but not in blood or normal tissue. Oncogenes were highly enriched on amplified ecDNA, and the most common recurrent oncogene amplifications arose on ecDNA. EcDNA amplifications resulted in higher levels of oncogene transcription compared to copy number-matched linear DNA, coupled with enhanced chromatin accessibility, and more frequently resulted in transcript fusions. Patients whose cancers carried ecDNA had significantly shorter survival, even when controlled for tissue type, than patients whose cancers were not driven by ecDNA-based oncogene amplification. The results presented here demonstrate that ecDNA-based oncogene amplification is common in cancer, is different from chromosomal amplification and drives poor outcome for patients across many cancer types.},
keywords = {Cell Line, Tumor
Chromatin/genetics
Chromosomes/*genetics
DNA/*genetics
Gene Amplification/*genetics
Humans
Neoplasms/*genetics
Oncogenes/*genetics},
ISSN = {1061-4036 (Print)
1061-4036},
DOI = {10.1038/s41588-020-0678-2},
year = {2020},
type = {Journal Article}
}
Downloads: 0
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