Mapping extrachromosomal DNA amplifications during cancer progression.
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
14 Oct 2024
14 Oct 2024
Historique:
received:
13
12
2023
accepted:
13
09
2024
medline:
15
10
2024
pubmed:
15
10
2024
entrez:
14
10
2024
Statut:
aheadofprint
Résumé
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.
Identifiants
pubmed: 39402156
doi: 10.1038/s41588-024-01949-7
pii: 10.1038/s41588-024-01949-7
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Cancer Research UK (CRUK)
ID : CGCATF-2021/100016
Organisme : Cancer Research UK (CRUK)
ID : CGCATF-2021/100025
Organisme : NCI NIH HHS
ID : R01 CA237208
Pays : United States
Organisme : NCI NIH HHS
ID : R33 CA236681
Pays : United States
Organisme : NCI NIH HHS
ID : R33 CA236681
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : OT2CA278635
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : U24CA264379
Organisme : National Research Foundation of Korea (NRF)
ID : NRF-2019R1A5A2027340
Organisme : National Research Foundation of Korea (NRF)
ID : NRF-2022M3C1A3092022
Organisme : Korea Health Industry Development Institute (KHIDI)
ID : HI19C1348
Informations de copyright
© 2024. The Author(s).
Références
Hanahan, D. Hallmarks of cancer: new dimensions. Cancer Discov. 12, 31–46 (2022).
doi: 10.1158/2159-8290.CD-21-1059
pubmed: 35022204
Seyfried, T. N. & Huysentruyt, L. C. On the origin of cancer metastasis. Crit. Rev. Oncog. 18, 43–73 (2013).
doi: 10.1615/CritRevOncog.v18.i1-2.40
pubmed: 23237552
pmcid: 3597235
Nguyen, B. et al. Genomic characterization of metastatic patterns from prospective clinical sequencing of 25,000 patients. Cell 185, 563–575 (2022).
doi: 10.1016/j.cell.2022.01.003
pubmed: 35120664
pmcid: 9147702
Martinez-Jimenez, F. et al. Pan-cancer whole-genome comparison of primary and metastatic solid tumours. Nature 618, 333–341 (2023).
doi: 10.1038/s41586-023-06054-z
pubmed: 37165194
pmcid: 10247378
Albertson, D. G. Gene amplification in cancer. Trends Genet. 22, 447–455 (2006).
doi: 10.1016/j.tig.2006.06.007
pubmed: 16787682
Verhaak, R. G. W., Bafna, V. & Mischel, P. S. Extrachromosomal oncogene amplification in tumour pathogenesis and evolution. Nat. Rev. Cancer 19, 283–288 (2019).
doi: 10.1038/s41568-019-0128-6
pubmed: 30872802
pmcid: 7168519
Yi, E., Chamorro Gonzalez, R., Henssen, A. G. & Verhaak, R. G. W. Extrachromosomal DNA amplifications in cancer. Nat. Rev. Genet. 23, 760–771 (2022).
doi: 10.1038/s41576-022-00521-5
pubmed: 35953594
pmcid: 9671848
Kim, H. et al. Extrachromosomal DNA is associated with oncogene amplification and poor outcome across multiple cancers. Nat. Genet. 52, 891–897 (2020).
doi: 10.1038/s41588-020-0678-2
pubmed: 32807987
pmcid: 7484012
Yi, E. et al. Live-cell imaging shows uneven segregation of extrachromosomal DNA elements and transcriptionally active extrachromosomal DNA hubs in cancer. Cancer Discov. 12, 468–483 (2021).
doi: 10.1158/2159-8290.CD-21-1376
pubmed: 34819316
pmcid: 8831456
Barker, P. E., Drwinga, H. L., Hittelman, W. N. & Maddox, A. M. Double minutes replicate once during S phase of the cell cycle. Exp. Cell Res. 130, 353–360 (1980).
doi: 10.1016/0014-4827(80)90012-9
pubmed: 7449855
deCarvalho, A. C. et al. Discordant inheritance of chromosomal and extrachromosomal DNA elements contributes to dynamic disease evolution in glioblastoma. Nat. Genet. 50, 708–717 (2018).
doi: 10.1038/s41588-018-0105-0
pubmed: 29686388
pmcid: 5934307
Zack, T. I. et al. Pan-cancer patterns of somatic copy number alteration. Nat. Genet. 45, 1134–1140 (2013).
doi: 10.1038/ng.2760
pubmed: 24071852
pmcid: 3966983
Koche, R. P. et al. Extrachromosomal circular DNA drives oncogenic genome remodeling in neuroblastoma. Nat. Genet. 52, 29–34 (2020).
doi: 10.1038/s41588-019-0547-z
pubmed: 31844324
Hung, K. L. et al. ecDNA hubs drive cooperative intermolecular oncogene expression. Nature 600, 731–736 (2021).
doi: 10.1038/s41586-021-04116-8
pubmed: 34819668
pmcid: 9126690
Wu, S. et al. Circular ecDNA promotes accessible chromatin and high oncogene expression. Nature 575, 699–703 (2019).
doi: 10.1038/s41586-019-1763-5
pubmed: 31748743
pmcid: 7094777
Shimizu, N., Itoh, N., Utiyama, H. & Wahl, G. M. Selective entrapment of extrachromosomally amplified DNA by nuclear budding and micronucleation during S phase. J. Cell Biol. 140, 1307–1320 (1998).
doi: 10.1083/jcb.140.6.1307
pubmed: 9508765
pmcid: 2132668
Von Hoff, D. D. et al. Elimination of extrachromosomally amplified MYC genes from human tumor cells reduces their tumorigenicity. Proc. Natl Acad. Sci. USA 89, 8165–8169 (1992).
doi: 10.1073/pnas.89.17.8165
Morton, A. R. et al. Functional enhancers shape extrachromosomal oncogene amplifications. Cell 179, 1330–1341 (2019).
doi: 10.1016/j.cell.2019.10.039
pubmed: 31761532
pmcid: 7241652
Helmsauer, K. et al. Enhancer hijacking determines extrachromosomal circular MYCN amplicon architecture in neuroblastoma. Nat. Commun. 11, 5823 (2020).
doi: 10.1038/s41467-020-19452-y
pubmed: 33199677
pmcid: 7669906
Priestley, P. et al. Pan-cancer whole-genome analyses of metastatic solid tumours. Nature 575, 210–216 (2019).
doi: 10.1038/s41586-019-1689-y
pubmed: 31645765
pmcid: 6872491
Barthel, F. P. et al. Longitudinal molecular trajectories of diffuse glioma in adults. Nature 576, 112–120 (2019).
doi: 10.1038/s41586-019-1775-1
pubmed: 31748746
pmcid: 6897368
Deshpande, V. et al. Exploring the landscape of focal amplifications in cancer using AmpliconArchitect. Nat. Commun. 10, 392 (2019).
doi: 10.1038/s41467-018-08200-y
pubmed: 30674876
pmcid: 6344493
Luebeck, J. et al. Extrachromosomal DNA in the cancerous transformation of Barrett’s oesophagus. Nature 616, 798–805 (2023).
doi: 10.1038/s41586-023-05937-5
pubmed: 37046089
pmcid: 10132967
Bergstrom, E. N. et al. Mapping clustered mutations in cancer reveals APOBEC3 mutagenesis of ecDNA. Nature 602, 510–517 (2022).
doi: 10.1038/s41586-022-04398-6
pubmed: 35140399
pmcid: 8850194
Hadi, K. et al. Distinct classes of complex structural variation uncovered across thousands of cancer genome graphs. Cell 183, 197–210 (2020).
doi: 10.1016/j.cell.2020.08.006
pubmed: 33007263
pmcid: 7912537
Roberts, S. A. et al. Clustered mutations in yeast and in human cancers can arise from damaged long single-strand DNA regions. Mol. Cell 46, 424–435 (2012).
doi: 10.1016/j.molcel.2012.03.030
pubmed: 22607975
pmcid: 3361558
Pich, O. et al. The mutational footprints of cancer therapies. Nat. Genet. 51, 1732–1740 (2019).
doi: 10.1038/s41588-019-0525-5
pubmed: 31740835
pmcid: 6887544
Nathanson, D. A. et al. Targeted therapy resistance mediated by dynamic regulation of extrachromosomal mutant EGFR DNA. Science 343, 72–76 (2014).
doi: 10.1126/science.1241328
pubmed: 24310612
Scribano, C. M. et al. Chromosomal instability sensitizes patient breast tumors to multipolar divisions induced by paclitaxel. Sci. Transl. Med. 13, eabd4811 (2021).
doi: 10.1126/scitranslmed.abd4811
pubmed: 34516829
pmcid: 8612166
Crasta, K. et al. DNA breaks and chromosome pulverization from errors in mitosis. Nature 482, 53–58 (2012).
doi: 10.1038/nature10802
pubmed: 22258507
pmcid: 3271137
Van de Haar, J. et al. Limited evolution of the actionable metastatic cancer genome under therapeutic pressure. Nat. Med. 27, 1553–1563 (2021).
doi: 10.1038/s41591-021-01448-w
pubmed: 34373653
Varn, F. S. et al. Glioma progression is shaped by genetic evolution and microenvironment interactions. Cell 185, 2184–2199 (2022).
doi: 10.1016/j.cell.2022.04.038
pubmed: 35649412
pmcid: 9189056
GLASS Consortium Glioma through the looking GLASS: molecular evolution of diffuse gliomas and the Glioma Longitudinal Analysis consortium. Neuro Oncol 20, 873–884 (2018).
doi: 10.1093/neuonc/noy020
Jamal-Hanjani, M. et al. Tracking the evolution of non-small-cell lung cancer. N. Engl. J. Med. 376, 2109–2121 (2017).
doi: 10.1056/NEJMoa1616288
pubmed: 28445112
Fitzgerald, D. M., Hastings, P. J. & Rosenberg, S. M. Stress-induced mutagenesis: implications in cancer and drug resistance. Annu. Rev. Cancer Biol. 1, 119–140 (2017).
doi: 10.1146/annurev-cancerbio-050216-121919
pubmed: 29399660
pmcid: 5794033
Tubbs, A. & Nussenzweig, A. Endogenous DNA damage as a source of genomic instability in cancer. Cell 168, 644–656 (2017).
doi: 10.1016/j.cell.2017.01.002
pubmed: 28187286
pmcid: 6591730
Shoshani, O. et al. Chromothripsis drives the evolution of gene amplification in cancer. Nature 591, 137–141 (2021).
doi: 10.1038/s41586-020-03064-z
pubmed: 33361815
Talevich, E., Shain, A. H., Botton, T. & Bastian, B. C. CNVkit: genome-wide copy number detection and visualization from targeted DNA sequencing. PLoS Comput. Biol. 12, e1004873 (2016).
doi: 10.1371/journal.pcbi.1004873
pubmed: 27100738
pmcid: 4839673
Bergstrom, E. N., Barnes, M., Martincorena, I. & Alexandrov, L. B. Generating realistic null hypothesis of cancer mutational landscapes using SigProfilerSimulator. BMC Bioinformatics 21, 438 (2020).
doi: 10.1186/s12859-020-03772-3
pubmed: 33028213
pmcid: 7539472
Bergstrom, E. N., Kundu, M., Tbeileh, N. & Alexandrov, L. B. Examining clustered somatic mutations with SigProfilerClusters. Bioinformatics 38, 3470–3473 (2022).
doi: 10.1093/bioinformatics/btac335
pubmed: 35595234
pmcid: 9237733