Cited by Ongoing chromothripsis underpins osteosarcoma genome complexity and clonal evolution

Chromothripsis as an on-target consequence of CRISPR–Cas9 genome editing DOI

Mitchell L. Leibowitz, Stamatis Papathanasiou, Phillip A. Doerfler

et al.

Nature Genetics, Journal Year: 2021, Volume and Issue: 53(6), P. 895 - 905

Published: April 12, 2021

Language: Английский

Citations

430

Extrachromosomal DNA is associated with oncogene amplification and poor outcome across multiple cancers DOI

Hoon Kim, Nam Nguyen, Kristen M. Turner

et al.

Nature Genetics, Journal Year: 2020, Volume and Issue: 52(9), P. 891 - 897

Published: Aug. 17, 2020

Language: Английский

Citations

412

Mutational signatures: emerging concepts, caveats and clinical applications DOI

Ching Chiek Koh, Andrea Degasperi, Xueqing Zou

et al.

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(10), P. 619 - 637

Published: July 27, 2021

Language: Английский

Citations

217

Causes and consequences of micronuclei DOI

Ksenia Krupina,

Alexander Goginashvili, Don W. Cleveland

et al.

Current Opinion in Cell Biology, Journal Year: 2021, Volume and Issue: 70, P. 91 - 99

Published: Feb. 21, 2021

Language: Английский

Citations

202

Cytoplasmic DNA: sources, sensing, and role in aging and disease DOI

Karl N. Miller, Stella Victorelli, Hanna Salmonowicz

et al.

Cell, Journal Year: 2021, Volume and Issue: 184(22), P. 5506 - 5526

Published: Oct. 1, 2021

Language: Английский

Citations

193

Spindle assembly checkpoint activation and silencing at kinetochores DOI

Pablo Lara-González, Jonathon Pines, Arshad Desai

et al.

Seminars in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 117, P. 86 - 98

Published: June 29, 2021

Language: Английский

Citations

191

Cancer evolution: Darwin and beyond DOI

Roberto Vendramin, Kevin Litchfield, Charles Swanton

et al.

The EMBO Journal, Journal Year: 2021, Volume and Issue: 40(18)

Published: Aug. 30, 2021

Review30 August 2021Open Access Cancer evolution: Darwin and beyond Roberto Vendramin orcid.org/0000-0001-7191-4887 Research UK Lung Centre of Excellence, University College London Institute, London, Search for more papers by this author Kevin Litchfield Corresponding Author [email protected] Charles Swanton Evolution Genome Instability Laboratory, The Francis Crick Information Vendramin1, *,1 *,1,2 1Cancer 2Cancer *Corresponding author. Tel: +44 207679 6500; E-mail: 203796 2047; EMBO Journal (2021)40:e108389https://doi.org/10.15252/embj.2021108389 This article is part the Reviews 2021 series. PDFDownload PDF text main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info Abstract Clinical laboratory studies over recent decades have established branched evolution as a feature cancer. However, while grounded in somatic selection, several lines evidence suggest Darwinian model alone insufficient fully explain cancer evolution. First, role macroevolutionary events tumour initiation progression contradicts Darwin's central thesis gradualism. Whole-genome doubling, chromosomal chromoplexy chromothripsis represent examples single catastrophic which can drive Second, neutral play some tumours, indicating that selection not always driving Third, increasing appreciation ageing soma has led generalised theories age-dependent carcinogenesis. Here, we review these concepts others, collectively argue extends Darwin. We also highlight clinical opportunities be grasped through targeting vulnerabilities arising from non-Darwinian patterns Introduction In his revolutionary work (Darwin, 1859), provided an evolutionary framework enabled understanding diversification extinction application three key concepts: variation, heredity selection. More than 100 years later, observation heterogeneity advanced malignancies Peter Nowell hypothesise tumorigenesis process, whereby same principles could applied elucidate mechanisms responsible formation development (Nowell, 1976). Owing Nowell's seminal work, been historically adopted develop models therapy resistance (Michor et al, 2004; Gatenby Vincent, 2008; Pepper 2009; Greaves Maley, 2012) (see Box 1). While gene-centric shown trajectories multiple instances (Gerlinger Swanton, 2010; Purushotham Sullivan, Gillies 2012), suggested additional are required reconcile full spectrum behaviours Specifically, now supports jumps (Stephens 2011; Baca 2013; Sottoriva 2015), likely interspaced phases microevolutionary Furthermore, discordant inheritance between cells (Decarvalho 2018), (Ling 2015; Williams 2016; Wu 2016), cell plasticity (Pogrebniak Curtis, 2018; Mills 2019; Boumahdi de Sauvage, 2020) microenvironment (Coussens Werb, 2002; Lin Karin, 2007; Laconi demand consideration broader set models. Understanding how influences disease such processes shaped environmental factors treatment remains critical. With review, discuss our process but light data, must incorporate into larger conceptual inclusive alternative approaches understand, predict better respond improve patient outcome. basis subclonal diversity viewed perspective (Greaves 2012). Indeed, tumours frequently typified large population genetically diverse giving rise distinct subpopulations. Subclones will compete with one another limited nutrients metabolites face ever-shifting selective pressures driven both endogenous (i.e. microenvironmental geographical barriers) exogenous therapy) (Merlo 2006). outcome competition survival clones adapted grow under very specific conditions, highly contextual blind future. Many were dominant at point time may reach dead ends disappear, only minority able persist. Quoting "One general law, leading advancement all organic beings, namely, multiply, vary, let strongest live weakest die" 1859). two decades, direct support reported, principally using next-generation sequencing (NGS) perform detailed characterisation genetic 2). One earliest was Shah al (2009), where matched primary metastatic tissue lobular breast sequenced revealing extensive mutational ∼80% non-synonymous mutations metastasis absent site (Shah 2009). finding pervasive additionally reported Kornelia Polyak, demonstrated composed variety types morphologies behaviours, source clonal (Campbell 2007). Early abundant, subpopulations revealed single-cell 2) Nick Navin others (Navin 2011). Regarding haematological malignancies, Anderson al. among first show branching acute lymphoblastic leukaemia (Anderson Our own Gerlinger (2012) profiled 30 samples four renal carcinoma patients 63 69% detectable across every region These observations extent relevance parallel suppressor genes (SETD2, PTEN, KDM5C), suggesting inactivation gene times within tumour. report followed Nik-Zainal (2012b), who studied life history 21 identifying variation individual (Nik-Zainal 2012b). study showed further each containing lineage, representing 50% cells. Extending detail on Gundem (2015) utilised autopsy sampling 10 prostate identify seeding common event (Gundem 2015). emphasised diversification, complexity routes sites. early small sample sizes. range meant nature patterns, generalisable or histology specific, remained undetermined. Despite limitations, NGS gave hence supporting growth (Fig demonstration solid spurred change thinking community recognise importance Branched applicable relatively homogeneous and/or metastases, particularly aggressive subclones achieve sweep present clinically profile (Reiter 2018) Clear described pancreatic cancer, virtually major driver alterations (KRAS, CDKN2A, TP53, SMAD4) most ancestor observed metastases (Makohon-Moore 2017). Similar carcinomas, ∼10–20% exhibit mutations, poor (Turajlic 2018). It proposed reflect differences inherent biology given impact upon dissemination (Iacobuzio-Donahue 2020). Figure 1. Models linear (A), (B), macroevolution (C) (D) Muller plots dynamic changes size (left), lineages phylogenetic trees (centre) number (right). Colours indicate different clones. Download figure PowerPoint accumulating subject pressure sufficient histories, points existence important features Macroevolution punctuated Neo-Darwinian generally assume acquired sequentially gradual fashion time. cases, genomic aberrations occur short bursts 2013), consequence instability (CIN) (Bakhoum Landau, 2017), breakage-fusion-bridge (BFB) cycles (Gisselsson 2000), (Baca Notta 2016) other similar According model, alternate long relative equilibrium periods intense evolution, acquire strong (Cross Such saltatory that, least certain circumstances make jumps, contrary what predicted. reminiscent "hopeful monsters" theorised Richard Goldschmidt, i.e. organisms profound mutant genotype compared their parents hold potential establish novel lineage (Goldschmidt, 1941). Hence, change, potentially obtain greater fitness would possible accumulation alterations, owing simultaneous acquisition (Korbel Campbell, 2013). phenotypic hereditary if any all, often deleterious rare it result increase cellular generation viable 1941; 2014b). 2. Scales Schematic illustration determinants influence interdependent mechanisms, microscopic (left) macroscopic (right) scale. death, implicates drivers progression. For example, prospective TRACERx (TRAcking (Rx)) (Jamal-Hanjani elevated copy identified being strongly associated recurrence/death risk non-small lung (NSCLC), whereas nucleotide variant non-significant. Similarly, aneuploidy detected recurrent gliomas (Barthel 2019), alongside (characterised high weighted genome integrity index (Endesfelder 2014)) emerged significant determinant clear (ccRCC) ccRCC, losses chromosomes 9p21.3 (CDKN2A) 14q31.1 (HIF1A) specifically reduced prognostic form (SCNAs), above becoming increasingly recognised pan-cancer phenomenon (Smith Sheltzer, A outstanding challenge however minimal mapping SCNA cytobands, find causative genes. And even when emerge, case CDKN2A 9p21 functional delineate precise completed. Additional occurring few cataclysmic events, termed chromoplexy, ER/PR/HER2 negative cancers found undergo remain stable later stages (Gao 2016). Tumour chromothripsis, thought complex rearrangements involving dozens breakpoints types, bone 2011), colon (Kloosterman neuroblastoma (Molenaar glioblastoma (Malhotra 2013) (Notta An extreme caused aforementioned "big bang" crises tumourigenesis numerous intermixed substantially evolve due weak (Sottoriva dynamics cancers, including 2015) hepatocellular well conceptually asexually reproducing organisms, terms cannot mitigated sexual reproduction. mechanism alleviate irreversible detrimental (e.g. LOH events) whole doubling (WGD), prevalent (Storchova Pellman, Zack Dewhurst 2014; Bielski entire genome. presence additional, doubled wild-type alleles WGD allow tolerate essential (López occurrence therefore creates tolerant permissive environment fuel rapid CIN, facilitate sub functionalisation duplicated Huminiecki Conant, 2012; 2014). Consequently, rates (Zack 2014) prognosis intrinsic drug (McGranahan Importantly, classes trigger events. instance, prone arise genomically unstable cells, those harbouring damaged telomeres hyperploidy (Mardin BFB generate amounts providing free DNA engage rearrangement compromising centromere function (Umbreit replication stress promoting structural numerical (Burrell triggering nucleotide-level mutagenesis mediated via APOBEC3B induction (Kanu turn leads incomplete (Venkatesan 2021). Relatedly, regional clusters (kataegis) 2011) lesion segregation (Aitken architectures 2012a). combination rapidly accelerates causing non-gradualism class itself would. Discordant Recent oncogene amplification extrachromosomal (ecDNA) frequent (Verhaak 2019). material outside autosomal recognised, reports oncogenic ecDNAs going back far 1980s, sequences resembling MYCN (Kohl 1983). last frequency started appreciated, thanks techniques long-read whole-genome circular library enrichment structures located variable (ranging 168 kb 5 Mb, median 1.26 Mb) (Wu contain oncogenes (Bailey provide maintain potent expression open chromatin, allows increased encoded counterparts Kim defies Mendelian genetics. replicated during S phase, but, lack centromeres, they unequal randomly inherited daughter mitosis. As such, ecDNA-based accelerate non-Mendelian expansion backgrounds random distribution fosters cell-to-cell variability transcriptional levels oncogenes, enabling ITH efficiently amplifications (Turner 2017; Verhaak Several ecDNA (albeit numbers) lung, (Fan Turner Deshpande Bailey 2020; Koche Key MYC, MYCN, EGFR, PDGFRA, MET, HER2, DHFR, CDK4 MDM2 ecDNAs, ecDNA-mediated Gu proliferation, invasion metastatisation negatively correlate overall elimination decrease affect (Shimizu 1998; Nathanson Clarke Oobatake Shimizu, enable adaptation response conditions Decarvalho 2020), though represents cancer-specific vulnerability (Nathanson Neutral based Motoo Kimura's genetics postulated vast majority molecular rather fixation selectively drift (Kimura, cancer-driving selected accumulate prior initiation, carcinogenic insults. Those development, little no contribution course Therefore, entirely (nearly) study, multi-region > 300 regions indicated there particular clone allele frequencies TCGA cohorts used conclude up one-third do indications (Williams results overestimation low resolution data suffer bias modelling, since abundance distributions enough information exclude (Tarabichi Bozic theory essentially states neutral, especially sizes purifying Most variants effect, ones predominantly deleterious, predicted mathematical modelling (Cannataro Kimura never excluded occasional positive applying changes, metastatisation, therapeutic intervention) taken consideration. treatment-naïve its progression, emergence forces, pressure, still previously (Almendro worth noting non-cell-autonomous give false impression (Marusyk Polyak's group subclone does higher fitness, instead stimulates scenario, misleading absence predominant relevant frames simultaneously fuelling Non-genetic There non-genetic—often non-heritable—determinants, (TME) (Caiado Ramón y Cajal Cell notion dynamically switch state stresses without gaining recognition (discussed reviews series Milan phenomenon, plasticity, characterised fundamental biological properties reversible epigenetic (in sharp contrast binary largely effects) (Calabrese advantages ability swiftly react finely tuned graded adaptive responses stressors inflammation (Rambow classic example epithelial–mesenchymal transition (EMT) (Nieto (extensively covered Brabletz (2021) series). genome, plethora phenotypes, promoted intervention (Kemper Gunnarsson Marine extensively escape pressure. identification drug-tolerant persisters (DTPs) emerging drug-sensitive NSCLC exposure EGFR tyrosine kinase inhibitor (Sharma 2010). phenotype transiently lost thereby demonstrating reversibly non-genetic switch. phenotypically distinct—yet interdependent—drug-tolerant populations recently emerge melanoma PDX MAPKi although resistant phenotypes non-heritable, protect eradication permanent melanoma, initially transient converted stably (Shaffer healthy tissues display genes, suggests malignant transformation (Martincorena 2015, Teixeira Yizhak Yoshida noted t

Language: Английский

Citations

181

ER-directed TREX1 limits cGAS activation at micronuclei DOI

Lisa Mohr, Eléonore Toufektchan, Patrick von Morgen

et al.

Molecular Cell, Journal Year: 2021, Volume and Issue: 81(4), P. 724 - 738.e9

Published: Jan. 20, 2021

Language: Английский

Citations

160

Genomic instability, inflammatory signaling and response to cancer immunotherapy DOI

Mengting Chen, Renske Linstra, Marcel A.T.M. van Vugt

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2021, Volume and Issue: 1877(1), P. 188661 - 188661

Published: Nov. 17, 2021

Genomic and chromosomal instability are hallmarks of cancer shape the genomic composition cells, thereby determining their behavior response to treatment. Various genetic epigenetic alterations in have been linked instability, including DNA repair defects, oncogene-induced replication stress, spindle assembly checkpoint malfunction. A consequence is leakage from nucleus into cytoplasm, either directly or through formation subsequent rupture micronuclei. Cytoplasmic subsequently activates cytoplasmic sensors, triggering downstream pathways, a type I interferon response. This inflammatory signaling has pleiotropic effects, enhanced anti-tumor immunity potentially results sensitization cells immune inhibitors. However, cancers frequently evolve mechanisms avoid clearance, suppression signaling. In this review, we summarize pathways induced by various sources adaptation that suppress signaling, implications for immunotherapy.

Language: Английский

Citations

124

Extrachromosomal circular DNA in cancer: history, current knowledge, and methods DOI

Julie B. Noer, Oskar Kjærgaard Hørsdal, Xi Xiang

et al.

Trends in Genetics, Journal Year: 2022, Volume and Issue: 38(7), P. 766 - 781

Published: March 8, 2022

Extrachromosomal circular DNA (eccDNA) has been described under different names at various times since the 1960s.eccDNA can be formed in cells as a result of cellular events and repair mechanisms contexts.Large eccDNA cancer is also called extrachromosomal (ecDNA). It amplify oncogenes rapidly contribute to their higher expression by more accessible chromatin novel contacts with enhancers.NGS-based methods have greatly accelerated our knowledge recent years; however, development cell animal models for functional studies needed.eccDNA ecDNA hold promise targets treatment or diagnostic procedures, but clinical value still needs determined. closed-circle, nuclear, nonplasmid molecule found all tested eukaryotes. plays important roles pathogenesis, evolution tumor heterogeneity, therapeutic resistance. known many names, including very large cancer-specific (ecDNA), which carries often amplified cells. Our understanding historically limited fragmented. To provide better context new previous research on eccDNA, this review we give an overview given times. We describe formation used study thus far. Finally, explore potential eccDNA. Healthy human somatic contain 23 pairs chromosomes form long, linear, condensable fibers. Besides mitochondrial genes, genetic information needed carry out functions. During mitosis, are replicated once resulting sister chromatids equally segregated, ensuring two genetically identical daughter cells.This normally tightly regulated mechanism disrupted genomes Cancers progress sequence mutational nucleotide substitutions, translocations, gene copy number gains losses that from environment genomic instability [1.Stratton M.R. et al.The genome.Nature. 2009; 2009: 719-724Crossref Scopus (2345) Google Scholar]. One most common changes tumorigenesis oncogene [2.Matsui A. al.Gene amplification: involvement cancer.Biomol. Concepts. 2013; 4: 567-582Crossref PubMed (63) Scholar], leading overexpression oncogenic products, provides growth advantages. The amplification not thoroughly understood, although it widely acknowledged underlying cause development. A major challenge current therapies such chemotherapy resistance drugs, ultimately therapy failure. Therapeutic depends biological properties populations stem-cell-like properties, regulation target molecules’ expression, activation prosurvival pathways, [3.Holohan C. al.Cancer drug resistance: evolving paradigm.Nat. Rev. Cancer. 13: 714-726Crossref (2915) Scholar].Circularization otherwise linear chromosomal one keys how amplifications arise. Circular molecules, plasmids, nuclei eukaryotic studied. This scientific literature covered below. content homologous nuclear DNA, derives [4.Wahl G.M. importance mammalian amplification.Cancer Res. 1989; 49: 1333-1340PubMed Scholar, 5.Gaubatz J.W. DNAs plasticity cells.Mutat. 1990; 237: 271-292Crossref (131) 6.Vogt N. al.Molecular structure double-minute bearing copies epidermal factor receptor gliomas.Proc. Natl. Acad. Sci. U. S. 2004; 101: 11368-11373Crossref (110) 7.Shibata Y. al.Extrachromosomal microDNAs microdeletions normal tissues.Science. 2012; 336: 82-86Crossref (137) 8.Turner K.M. drives tumour heterogeneity.Nature. 2017; 543: 122-125Crossref (281) 9.Møller H.D. al.Circular elements origin healthy tissue.Nat. Commun. 2018; 9: 1069Crossref (107) vary size less than 100 bp several megabases, any element genome small, noncoding regions entire genes [7.Shibata was observed first time boar sperm wheat embryos 1964 when Hotta Bassel investigated using electron microscopy theory organisms made circles [10.Hotta Molecular circularity mammals plants.Proc. 1965; 53: 356-362Crossref (101) Later 1960s 1970s, filamentous fungi yeast well birds variety tissues, suggesting phenomenon [5.Gaubatz majority identified these too small (<500 bp) whole protein-coding [11.Smith C.A. Vinograd J. Small polydisperse HeLa cells.J. Mol. Biol. 1972; 69: 163-178Crossref (106) In cells, much larger structures were discovered approximately same through staining light microscopic examination metaphase [12.Cox D. al.Minute bodies malignant tumours childhood.Lancet. 1: 55-58Abstract (157) These initially denoted double minutes (DMs) due (in relation chromosomes) distinct pairing metaphase. DMs enough [13.Cowell J.K. Double homogeneously regions: cells.Annu. Genet. 1982; 16: 21-59Crossref (268) Later, sequencing junction points supported circularization relative [6.Vogt Scholar].Pioneering work Wahl others revealed tumors close link between cancers recently become even clear. influential paper 2017, proportion types megabase-size specifically [8.Turner complemented reports showing evolves neurological [14.Morton A.R. al.Functional enhancers shape amplifications.Cell. 2019; 179: 1330-1341.e1313Abstract Full Text PDF (102) Scholar,15.Helmsauer K. al.Enhancer hijacking determines MYCN amplicon architecture neuroblastoma.Nat. 2020; 11: 5823Crossref (50) Scholar] some associated mortality [16.Koche R.P. remodeling 52: 29-34Crossref (97) Scholar,17.Kim H. poor outcome across multiple cancers.Nat. 891-897Crossref (95) Scholar].Although eccDNAs sizes elements, according Scholar,16.Koche Scholar,18.Mehanna P. al.Characterization microDNA response chemotherapeutics lymphoblastoid lines.PLoS One. 12e0184365Crossref (19) focused ecDNAs Scholar,8.Turner Scholar,14.Morton Scholar,19.deCarvalho A.C. al.Discordant inheritance contributes dynamic disease glioblastoma.Nat. 50: 708-717Crossref (121) little mixtures thousands arise affect progression, whether biomarker. review, named contexts. then generated maintained field finally discuss use marker diagnosis, prognosis, cancer.Nomenclature definitionseccDNAHistorically, isolated types, led names. suggested term cover endogenous 1990 Scholar].Covalently closed DNAIn earliest describing covalently sometimes used. double-stranded viral genomes, bacterial Scholar,20.Radloff R. al.A dye-buoyant-density method detection isolation duplex DNA: cells.Proc. 1967; 57: 1514-1521Crossref (856) now mostly virology.Small DNAThe name (spcDNA) density separation visualized 1972 spcDNA smaller end spectrum (<100–10 000 until 2000s. comes heterogeneous distribution Scholar,11.Smith mainly containing repetitive sequences could reflect analysis available rather true frequency repeat spcDNA. abundant unstable patients Fanconi’s anemia [21.Cohen al.Small polydispersed cells: association instability.Oncogene. 1997; 14: 977-985Crossref (80) Scholar,22.Cohen Z. al.Mouse satellite prone via Ligase IV-dependent pathway.Oncogene. 2006; 25: 4515-4524Crossref (37) Scholar].microDNAThe arose 2012 circularized mouse lines purification vast determined 200 3000 [23.Paulsen T. al.Discoveries cells.Trends 34: 270-278Abstract Thus, terms molecules similar physical properties. Sequencing they parts genome, though 5′ 3′ termini GC appears overrepresented compared Scholar].The functions well-elucidated. makes them unable full promoter regions. 2019 express regulatory RNA, microRNA (miRNA) interfering RNA [24.Paulsen DNAs, microDNA, produce short RNAs suppress independent canonical promoters.Nucleic Acids 47: 4586-4596Crossref (31) authors transcribed without promoter. results suggest regulate transcription RNA. Although individuals, length varies sample tissue, plasma, [9.Møller Scholar,25.Kumar al.Normal cancerous tissues release into circulation.Mol. Cancer 15: 1197-1205Crossref (94) Scholar,26.Sin S.T.K. al.Identification characterization maternal plasma.Proc. 117: 1658-1665Crossref (46) Scholar].Telomeric circlesTelomeric specialized group immortalization telomerase-negative alternative lengthening telomeres (ALT) [27.Reddel R.R. Alternative telomeres, telomerase, cancer.Cancer Lett. 2003; 194: 155-162Crossref Telomeric serve templates telomere elongation ALT reported responsible maintenance 10–15% [28.Zhao al.Alternative pluripotent stem cells.Genes (Basel). 10Crossref (17) t circles, fully telomeric repeats, c partially single-stranded C-rich region. Electron shown 30 [29.Basenko E.Y. al.Telomeric stn1-M1 mutant maintains its recombination.Nucleic 2010; 38: 182-189Crossref (15) osteosarcoma, soft tissue sarcoma, glioblastoma multiforme (GBM), renal carcinoma, adrenocortical breast non-small lung ovarian carcinoma Scholar].DMsLarge megabase range Cox al. 1965, examined spreads childhood paired bodies, species recognizable centromeres Scholar,30.Lin C.C. al.Apparent lack minute chromosomes.Cancer Cytogenet. 48: 271-274Abstract (14) role overexpression. They tend accumulate advantage Scholar].EpisomesIn 1980s, autonomously replicating submicroscopic range. episomes [31.Carroll S.M. episome produced hamster transfected CAD high frequency: evidence replication origin.Mol. Cell. 1987; 7: 1740-1750Crossref Episomes denaturation renaturation gel electrophoresis. model genetics states excision followed Scholar,32.Carroll al.Double precursors derived deletion.Mol. 1988; 8: 1525-1533Crossref (173) 33.Storlazzi C.T. al.MYC-containing hematologic malignancies: favor exclusion MYC gene.Hum. 933-942Crossref 34.Storlazzi solid tumors: structure.Genome 20: 1198-1206Crossref (132) Scholar].ecDNANext-generation (NGS)-based years allowed scientists in-depth. definition mega-base-pair cancer, namely broad 46% 17 types. especially GBM prostate, breast, lung, melanoma Scholar].In following text, previously defined classes eukaryotic, nonmitochondrial, DNA. will subset oncogenes, DMs. Since generally studied separately, findings only considered valid subsets. therefore chosen differentiate what about formation, relevance ecDNA, respectively.Formation maintenanceFormationA exist involve damage erroneous actions pathways. For example, double-strand breaks (DSBs) chromosome stretch deleted, (Figure 1A ), secondary loop processes, mismatch (MMR) (see Glossary), excised [35.Dillon L.W. al.Production linked pathways transcriptional activity.Cell Rep. 2015; 1749-1759Abstract (73) 36.Møller yeast.Proc. 112: E3114-E3122Crossref (115) 37.Paulsen al.MicroDNA levels dependent MMEJ, repressed c-NHEJ pathway, stimulated damage.Nucleic 2021; 11787-11799Crossref (7) Therefore, depending where subjected active cell.In studies, sequenced junctions likely them. Junctions indicate homology not. no nonhomologous joining (NHEJ) 1A) [38.Weterings E. Chen D.J. endless tale non-homologous end-joining.Cell 2008; 18: 114-124Crossref (283) organism Saccharomyces cerevisiae (baker’s yeast) Scholar,35.Dillon Scholar,36.Møller Scholar,39.van Loon al.Formation 1994; 22: 2447-2452Crossref (36) Scholar,40.L’Abbate al.Genomic organization minutes/homogeneously cancer.Nucleic 2014; 42: 9131-9145Crossref (75) directly validate DSBs, clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 create DSBs chromosome. Subsequently, happened [41.Møller al.CRISPR-C: CRISPR cells.Nucleic 46e131Google There forming homology, potentially recombination (HR) [36.Møller Scholar,42.Sinclair D.A. Guarente L. rDNA circles--a aging yeast.Cell. 91: 1033-1042Abstract (1162) 43.Gresham al.Adaptation diverse nitrogen-limited environments deletion GAP1 locus.Proc. 107: 18551-18556Crossref 44.Hull R.M. al.Transcription-induced during ageing.PLoS 17e3000471Crossref (38) 45.Prada-Luengo I. al.Replicative loss heterogeneity cerevisiae.Nucleic 7883-7898Crossref (8) newer cerevisiae, early reviewed Gaubatz HR expected rare, primarily mitosis postmitotic, NHEJ primary DSBs. indeed minority repeatedly loci Scholar].NGS-based may underestimate effec

Language: Английский

Citations

108