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Examining the role of extrachromosomal DNA in 1,216 lung cancers

Khandekar, A.
; 
Hoang, P. H.
; 
Luebeck, J.
; 
Díaz-Gay, M.
; 
Zhao, W.
; 
McElderry, J. P.
; 
Hartman, C.
; 
Miraftab, M.
; 
Lee, O. W.
; 
Barnao, K. M.
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Abstract
The role of extrachromosomal DNA (ecDNA) in lung cancer, particularly in subjects who never smoked (LCINS), remains unclear. Examination of 1,216 whole-genome-sequenced lung cancers identified ecDNA in 18.9% of patients. Recurrent amplification of MDM2 and other oncogenes via ecDNA possibly drives a LCINS subset. Tumors harboring ecDNA showed worse overall survival than tumors harboring other focal amplifications. A strong association with whole-genome doubling suggests most ecDNA reflects genomic instability in treatment-naïve lung cancer.
Authors
Khandekar, A.
Hoang, P. H.
Luebeck, J.
Díaz-Gay, M.
Zhao, W.
McElderry, J. P.
Hartman, C.
Miraftab, M.
Lee, O. W.
Barnao, K. M.
Bergstrom, E. N.
Yang, Y.
Nowak, M. A.
Rothman, N.
Homer, R.
Yang, S. R.
Lan, Q.
Wedge, D. C.
Yang, L.
Chanock, S. J.
Zhang, T.
Alexandrov, L. B.
Landi, M. T.
Affiliation
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA. Department of Bioengineering, University of California San Diego, La Jolla, CA, USA. Moores Cancer Center, University of California San Diego, La Jolla, CA, USA. Department of Computer Science, University of California San Diego, La Jolla, CA, USA. Digital Genomics Group, Structural Biology Program, Spanish National Cancer Research Center (CNIO), Madrid, Spain. Ben May Department for Cancer Research, The University of Chicago, Chicago, IL, USA. Department of Mathematics, Harvard University, Cambridge, MA, USA. Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA. Department of Pathology, Yale School of Medicine, New Haven, CT, USA. Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Manchester Cancer Research Centre, The University of Manchester, Manchester, UK. Manchester NIHR Biomedical Research Centre, Manchester, UK. Department of Human Genetics, The University of Chicago, Chicago, IL, USA. The University of Chicago Medicine Comprehensive Cancer Center, The University of Chicago, Chicago, IL, USA. Sanford Stem Cell Institute, University of California San Diego, La Jolla, CA, USA.
Description
Date
2025
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All Paterson Institute for Cancer Research
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Preprint
Citation
Khandekar A, Hoang PH, Luebeck J, Díaz-Gay M, Zhao W, McElderry JP, et al. Examining the Role of Extrachromosomal DNA in 1,216 Lung Cancers. BioRxiv : the preprint server for biology. 2025 Jul 24. PubMed PMID: 40501879. Pubmed Central PMCID: PMC12157361 consultant for io9, has equity and receives income. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies. LBA is a compensated member of the scientific advisory board of Inocras. LBA’s spouse is an employee of Hologic, Inc. LBA declares U.S. provisional applications with serial numbers: 63/289,601; 63/269,033; 63/366,392; 63/412,835 as well as international patent application PCT/US2023/010679. LBA is also an inventor of a US Patent 10,776,718 for source identification by non-negative matrix factorization. LBA and MD-G further declare a European patent application with application number EP25305077.7. Soo-Ryum Yang has received speaking fees from Medscape, OncLive, Cure Today, Medical Learning Institute, PRIME Education, AstraZeneca, Roche; and consulting fees from AstraZeneca, AbbVie, Merus, Eli Lilly, Boehringer Ingelheim, Roche, Amgen, Sanofi. All other authors declare no conflicts of interest. Epub 2025/06/12. eng.
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https://christie.openrepository.com/handle/10541/627729
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