Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Mechanisms driving chromosomal translocations: lost in time and space

Oncogene volume 40, pages 4263–4270 (2021)Cite this article

Subjects

Abstract

Translocations arise when an end of one chromosome break is mistakenly joined to an end from a different chromosome break. Since translocations can lead to developmental disease and cancer, it is important to understand the mechanisms leading to these chromosome rearrangements. We review how characteristics of the sources and the cellular responses to chromosome breaks contribute to the accumulation of multiple chromosome breaks at the same moment in time. We also discuss the important role for chromosome break location; how translocation potential is impacted by the location of chromosome breaks both within chromatin and within the nucleus, as well as the effect of altered mobility of chromosome breaks. A common theme in work addressing both temporal and spatial contributions to translocation is that there is no shortage of examples of factors that promote translocation in one context, but have no impact or the opposite impact in another. Accordingly, a clear message for future work on translocation mechanism is that unlike normal DNA metabolic pathways, it isn’t easily modeled as a simple, linear pathway that is uniformly followed regardless of differing cellular contexts.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Causes of chromosomal translocations.
Fig. 2: The role of DNA repair in translocation.

Similar content being viewed by others

References

  1. Li Y, Roberts ND, Wala JA, Shapira O, Schumacher SE, Kumar K, et al. Patterns of somatic structural variation in human cancer genomes. Nature. 2020;578:112–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Zhang F, Khajavi M, Connolly AM, Towne CF, Batish SD, Lupski JR. The DNA replication FoSTeS/MMBIR mechanism can generate genomic, genic and exonic complex rearrangements in humans. Nat Genet. 2009;41:849–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Sakofsky CJ, Malkova A. Break induced replication in eukaryotes: mechanisms, functions, and consequences. Crit Rev Biochem Mol Biol. 2017;52:395–413.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Sudmant PH, Rausch T, Gardner EJ, Handsaker RE, Abyzov A, Huddleston J, et al. An integrated map of structural variation in 2,504 human genomes. Nature. 2015;526:75–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Gao S, Honey S, Futcher B, Grollman AP. The non-homologous end-joining pathway of S. cerevisiae works effectively in G1-phase cells, and religates cognate ends correctly and non-randomly. DNA Repair (Amst). 2016;42:1–10.

    Article  Google Scholar 

  6. Lee K, Zhang Y, Lee SE. Saccharomyces cerevisiae ATM orthologue suppresses break-induced chromosome translocations. Nature. 2008;454:543–6.

    Article  CAS  PubMed  Google Scholar 

  7. Richardson C, Moynahan ME, Jasin M. Double-strand break repair by interchromosomal recombination: suppression of chromosomal translocations. Genes Dev. 1998;12:3831–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Zhang Y, McCord RP, Ho YJ, Lajoie BR, Hildebrand DG, Simon AC, et al. Spatial organization of the mouse genome and its role in recurrent chromosomal translocations. Cell. 2012;148:908–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Vilenchik MM, Knudson AG. Endogenous DNA double-strand breaks: production, fidelity of repair, and induction of cancer. Proc Natl Acad Sci USA. 2003;100:12871–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lobrich M, Cooper PK, Rydberg B. Joining of correct and incorrect DNA ends at double-strand breaks produced by high-linear energy transfer radiation in human fibroblasts. Radiat Res. 1998;150:619–26.

    Article  CAS  PubMed  Google Scholar 

  11. Brunet E, Jasin M. Induction of chromosomal translocations with CRISPR-Cas9 and other nucleases: understanding the repair mechanisms that give rise to translocations. Adv Exp Med Biol. 2018;1044:15–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Morton LM, Karyadi DM, Stewart C, Bogdanova TI, Dawson ET, Steinberg MK, et al. Radiation-related genomic profile of papillary thyroid carcinoma after the Chernobyl accident. Science. 2021;372:eabg2538.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Waters CA, Strande NT, Wyatt DW, Pryor JM, Ramsden DA. Nonhomologous end joining: a good solution for bad ends. DNA Repair (Amst). 2014;17:39–51.

    Article  CAS  Google Scholar 

  14. Ramsden DA, Gellert M. Formation and resolution of double-strand break intermediates in V(D)J rearrangement. Genes Dev. 1995;9:2409–20.

    Article  CAS  PubMed  Google Scholar 

  15. Ramsden DA, Paull TT, Gellert M. Cell-free V(D)J recombination. Nature. 1997;388:488–91.

    Article  CAS  PubMed  Google Scholar 

  16. Pannunzio NR, Lieber MR. Concept of DNA lesion longevity and chromosomal translocations. Trends Biochem Sci. 2018;43:490–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Sternberg SH, Redding S, Jinek M, Greene EC, Doudna JA. DNA interrogation by the CRISPR RNA-guided endonuclease Cas9. Nature. 2014;507:62–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Richardson CD, Ray GJ, DeWitt MA, Curie GL, Corn JE. Enhancing homology-directed genome editing by catalytically active and inactive CRISPR-Cas9 using asymmetric donor DNA. Nat Biotechnol. 2016;34:339–44.

    Article  CAS  PubMed  Google Scholar 

  19. Stracker TH, Petrini JH. The MRE11 complex: starting from the ends. Nat Rev Mol Cell Biol. 2011;12:90–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Bredemeyer AL, Huang CY, Walker LM, Bassing CH, Sleckman BP. Aberrant V(D)J recombination in ataxia telangiectasia mutated-deficient lymphocytes is dependent on nonhomologous DNA end joining. J Immunol. 2008;181:2620–5.

    Article  CAS  PubMed  Google Scholar 

  21. Chen C, Kolodner RD. Gross chromosomal rearrangements in Saccharomyces cerevisiae replication and recombination defective mutants. Nat Genet. 1999;23:81–5.

    Article  CAS  PubMed  Google Scholar 

  22. Gunn A, Bennardo N, Cheng A, Stark JM. Correct end use during end joining of multiple chromosomal double strand breaks is influenced by repair protein RAD50, DNA-dependent protein kinase DNA-PKcs, and transcription context. J Biol Chem. 2011;286:42470–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Bredemeyer AL, Sharma GG, Huang CY, Helmink BA, Walker LM, Khor KC, et al. ATM stabilizes DNA double-strand-break complexes during V(D)J recombination. Nature. 2006;442:466–70.

    Article  CAS  PubMed  Google Scholar 

  24. Callen E, Jankovic M, Difilippantonio S, Daniel JA, Chen HT, Celeste A, et al. ATM prevents the persistence and propagation of chromosome breaks in lymphocytes. Cell. 2007;130:63–75.

    Article  CAS  PubMed  Google Scholar 

  25. Bunting SF, Nussenzweig A. End-joining, translocations and cancer. Nat Rev Cancer. 2013;13:443–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Caldecott KW. Protein ADP-ribosylation and the cellular response to DNA strand breaks. DNA Repair (Amst). 2014;19:108–13.

    Article  CAS  Google Scholar 

  27. Fisher AE, Hochegger H, Takeda S, Caldecott KW Poly(ADP-ribose) polymerase 1 accelerates single-strand break repair in concert with poly(ADP-ribose) glycohydrolase. Mol Cell Biol. 2007; 27: 5597–605.

  28. Audebert M, Salles B, Calsou P Involvement of poly(ADP-ribose) polymerase-1 and XRCC1/DNA ligase III in an alternative route for DNA double-strand breaks rejoining. J Biol Chem. 2004; 279: 55117–26.

  29. Rulten SL, Fisher AE, Robert I, Zuma MC, Rouleau M, Ju L, et al. PARP-3 and APLF function together to accelerate nonhomologous end-joining. Mol Cell. 2011;41:33–45.

    Article  CAS  PubMed  Google Scholar 

  30. Layer JV, Cleary JP, Brown AJ, Stevenson KE, Morrow SN, Van Scoyk A, et al. Parp3 promotes long-range end joining in murine cells. Proc Natl Acad Sci USA. 2018;115:10076–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wray J, Williamson EA, Singh SB, Wu Y, Cogle CR, Weinstock DM, et al. PARP1 is required for chromosomal translocations. Blood. 2013;121:4359–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Day TA, Layer JV, Cleary JP, Guha S, Stevenson KE, Tivey T, et al. PARP3 is a promoter of chromosomal rearrangements and limits G4 DNA. Nat Commun. 2017;8:15110.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Scully R, Panday A, Elango R, Willis NA. DNA double-strand break repair-pathway choice in somatic mammalian cells. Nat Rev Mol Cell Biol. 2019;20:698–714.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Richardson C, Jasin M. Coupled homologous and nonhomologous repair of a double-strand break preserves genomic integrity in mammalian cells. Mol Cell Biol. 2000;20:9068–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Boboila C, Jankovic M, Yan CT, Wang JH, Wesemann DR, Zhang T, et al. Alternative end-joining catalyzes robust IgH locus deletions and translocations in the combined absence of ligase 4 and Ku70. Proc Natl Acad Sci USA. 2010;107:3034–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Boboila C, Yan C, Wesemann DR, Jankovic M, Wang JH, Manis J, et al. Alternative end-joining catalyzes class switch recombination in the absence of both Ku70 and DNA ligase 4. J Exp Med. 2010;207:417–27.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Difilippantonio MJ, Zhu J, Chen HT, Meffre E, Nussenzweig MC, Max EE, et al. DNA repair protein Ku80 suppresses chromosomal aberrations and malignant transformation. Nature. 2000;404:510–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Weinstock DM, Brunet E, Jasin M. Formation of NHEJ-derived reciprocal chromosomal translocations does not require Ku70. Nat Cell Biol. 2007;9:978–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Simsek D, Brunet E, Wong SY, Katyal S, Gao Y, McKinnon PJ, et al. DNA ligase III promotes alternative nonhomologous end-joining during chromosomal translocation formation. PLoS Genet. 2011;7:e1002080.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Zhang Y, Jasin M. An essential role for CtIP in chromosomal translocation formation through an alternative end-joining pathway. Nat Struct Mol Biol. 2011;18:80–4.

    Article  CAS  PubMed  Google Scholar 

  41. Ghezraoui H, Piganeau M, Renouf B, Renaud JB, Sallmyr A, Ruis B, et al. Chromosomal translocations in human cells are generated by canonical nonhomologous end-joining. Mol Cell. 2014;55:829–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Anderson CW, Lees-Miller SP. The nuclear serine/threonine protein kinase DNA-PK. Crit Rev Eukaryot Gene Expr. 1992;2:283–314.

    CAS  PubMed  Google Scholar 

  43. Tuteja R, Tuteja N. Ku autoantigen: a multifunctional DNA-binding protein. Crit Rev Biochem Mol Biol. 2000;35:1–33.

    Article  CAS  PubMed  Google Scholar 

  44. Mateos-Gomez PA, Gong F, Nair N, Miller KM, Lazzerini-Denchi E, Sfeir A. Mammalian polymerase theta promotes alternative NHEJ and suppresses recombination. Nature. 2015;518:254–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Yousefzadeh MJ, Wyatt DW, Takata K, Mu Y, Hensley SC, Tomida J, et al. Mechanism of suppression of chromosomal instability by DNA polymerase POLQ. PLoS Genet. 2014;10:e1004654.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Shima N, Munroe RJ, Schimenti JC. The mouse genomic instability mutation chaos1 is an allele of Polq that exhibits genetic interaction with Atm. Mol Cell Biol. 2004;24:10381–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Wyatt DW, Feng W, Conlin MP, Yousefzadeh MJ, Roberts SA, Mieczkowski P, et al. Essential roles for polymerase theta-mediated end joining in the repair of chromosome breaks. Mol Cell. 2016;63:662–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Yu W, Lescale C, Babin L, Bedora-Faure M, Lenden-Hasse H, Baron L, et al. Repair of G1 induced DNA double-strand breaks in S-G2/M by alternative NHEJ. Nat Commun. 2020;11:5239.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Liang Z, Kumar V, Le Bouteiller M, Zurita J, Kenrick J, Lin SG et al. Ku70 suppresses alternative end-joining in G1-arrested progenitor B cells. bioRxiv 2021: 2021.2002.2020.432121.

  50. Carvajal-Garcia J, Cho JE, Carvajal-Garcia P, Feng W, Wood RD, Sekelsky J, et al. Mechanistic basis for microhomology identification and genome scarring by polymerase theta. Proc Natl Acad Sci USA. 2020;117:8476–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Kramara J, Osia B, Malkova A. Break-induced replication: the where, the why, and the how. Trends Genet. 2018;34:518–31.

    Article  CAS  PubMed  Google Scholar 

  52. Pannunzio NR, Li S, Watanabe G, Lieber MR. Non-homologous end joining often uses microhomology: implications for alternative end joining. DNA Repair (Amst). 2014;17:74–80.

    Article  CAS  Google Scholar 

  53. Lu G, Duan J, Shu S, Wang X, Gao L, Guo J, et al. Ligase I and ligase III mediate the DNA double-strand break ligation in alternative end-joining. Proc Natl Acad Sci USA. 2016;113:1256–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Hanzlikova H, Gittens W, Krejcikova K, Zeng Z, Caldecott KW. Overlapping roles for PARP1 and PARP2 in the recruitment of endogenous XRCC1 and PNKP into oxidized chromatin. Nucleic Acids Res. 2017;45:2546–57.

    CAS  PubMed  Google Scholar 

  55. Pommier Y, Sun Y, Huang SN, Nitiss JL. Roles of eukaryotic topoisomerases in transcription, replication and genomic stability. Nat Rev Mol Cell Biol. 2016;17:703–21.

    Article  CAS  PubMed  Google Scholar 

  56. Muntean AG, Hess JL. The pathogenesis of mixed-lineage leukemia. Annu Rev Pathol. 2012;7:283–301.

    Article  CAS  PubMed  Google Scholar 

  57. Canela A, Maman Y, Huang SN, Wutz G, Tang W, Zagnoli-Vieira G, et al. Topoisomerase II-induced chromosome breakage and translocation is determined by chromosome architecture and transcriptional activity. Mol Cell. 2019;75:252–66. e258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Gothe HJ, Bouwman BAM, Gusmao EG, Piccinno R, Petrosino G, Sayols S, et al. Spatial chromosome folding and active transcription drive DNA fragility and formation of oncogenic MLL translocations. Mol Cell. 2019;75:267–83. e212

    Article  CAS  PubMed  Google Scholar 

  59. Gomez-Herreros F, Zagnoli-Vieira G, Ntai I, Martinez-Macias MI, Anderson RM, Herrero-Ruiz A, et al. TDP2 suppresses chromosomal translocations induced by DNA topoisomerase II during gene transcription. Nat Commun. 2017;8:233.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Canela A, Maman Y, Jung S, Wong N, Callen E, Day A, et al. Genome organization drives chromosome fragility. Cell. 2017;170:507–21. e518.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Uuskula-Reimand L, Hou H, Samavarchi-Tehrani P, Rudan MV, Liang M, Medina-Rivera A, et al. Topoisomerase II beta interacts with cohesin and CTCF at topological domain borders. Genome Biol. 2016;17:182.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Lobachev K, Vitriol E, Stemple J, Resnick MA, Bloom K. Chromosome fragmentation after induction of a double-strand break is an active process prevented by the RMX repair complex. Curr Biol. 2004;14:2107–12.

    Article  CAS  PubMed  Google Scholar 

  63. Soutoglou E, Dorn JF, Sengupta K, Jasin M, Nussenzweig A, Ried T, et al. Positional stability of single double-strand breaks in mammalian cells. Nat Cell Biol. 2007;9:675–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Roix JJ, McQueen PG, Munson PJ, Parada LA, Misteli T. Spatial proximity of translocation-prone gene loci in human lymphomas. Nat Genet. 2003;34:287–91.

    Article  CAS  PubMed  Google Scholar 

  65. Roukos V, Voss TC, Schmidt CK, Lee S, Wangsa D, Misteli T. Spatial dynamics of chromosome translocations in living cells. Science. 2013;341:660–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Sunder S, Wilson TE. Frequency of DNA end joining in trans is not determined by the predamage spatial proximity of double-strand breaks in yeast. Proc Natl Acad Sci USA. 2019;116:9481–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Dion V, Kalck V, Horigome C, Towbin BD, Gasser SM. Increased mobility of double-strand breaks requires Mec1, Rad9 and the homologous recombination machinery. Nat Cell Biol. 2012;14:502–9.

    Article  CAS  PubMed  Google Scholar 

  68. Mine-Hattab J, Rothstein R. Increased chromosome mobility facilitates homology search during recombination. Nat Cell Biol. 2012;14:510–7.

    Article  CAS  PubMed  Google Scholar 

  69. Krawczyk PM, Borovski T, Stap J, Cijsouw T, ten Cate R, Medema JP, et al. Chromatin mobility is increased at sites of DNA double-strand breaks. J Cell Sci. 2012;125:2127–33.

    CAS  PubMed  Google Scholar 

  70. Kruhlak MJ, Celeste A, Dellaire G, Fernandez-Capetillo O, Muller WG, McNally JG, et al. Changes in chromatin structure and mobility in living cells at sites of DNA double-strand breaks. J Cell Biol. 2006;172:823–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Dimitrova N, Chen YC, Spector DL, de Lange T. 53BP1 promotes non-homologous end joining of telomeres by increasing chromatin mobility. Nature. 2008;456:524–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Lottersberger F, Karssemeijer RA, Dimitrova N, de Lange T. 53BP1 and the LINC complex promote microtubule-dependent DSB mobility and DNA repair. Cell. 2015;163:880–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Difilippantonio S, Gapud E, Wong N, Huang CY, Mahowald G, Chen HT, et al. 53BP1 facilitates long-range DNA end-joining during V(D)J recombination. Nature. 2008;456:529–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Cho NW, Dilley RL, Lampson MA, Greenberg RA. Interchromosomal homology searches drive directional ALT telomere movement and synapsis. Cell. 2014;159:108–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Aten JA, Stap J, Krawczyk PM, van Oven CH, Hoebe RA, Essers J, et al. Dynamics of DNA double-strand breaks revealed by clustering of damaged chromosome domains. Science. 2004;303:92–5.

    Article  CAS  PubMed  Google Scholar 

  76. Aymard F, Aguirrebengoa M, Guillou E, Javierre BM, Bugler B, Arnould C, et al. Genome-wide mapping of long-range contacts unveils clustering of DNA double-strand breaks at damaged active genes. Nat Struct Mol Biol. 2017;24:353–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Schrank BR, Aparicio T, Li Y, Chang W, Chait BT, Gundersen GG, et al. Nuclear ARP2/3 drives DNA break clustering for homology-directed repair. Nature. 2018;559:61–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Whalen JM, Dhingra N, Wei L, Zhao X, Freudenreich CH. Relocation of collapsed forks to the nuclear pore complex depends on sumoylation of DNA repair proteins and permits Rad51 association. Cell Rep. 2020;31:107635.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Caridi CP, D’Agostino C, Ryu T, Zapotoczny G, Delabaere L, Li X, et al. Nuclear F-actin and myosins drive relocalization of heterochromatic breaks. Nature. 2018;559:54–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

D.A.R’s laboratory was supported by NCI grants CA222092 and CA097096 and DOD grant W81XWH-18-1-004. The A.N. laboratory is supported by the Intramural Research Program of the NIH.

Author information

Authors and Affiliations

  1. Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Dale A. Ramsden

  2. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Dale A. Ramsden

  3. Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Dale A. Ramsden

  4. Laboratory of Genome Integrity, National Institutes of Health, Bethesda, USA

    Andre Nussenzweig

Authors
  1. Dale A. Ramsden
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andre Nussenzweig
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dale A. Ramsden.

Ethics declarations

Conflict of interest

The authors declare no competing interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ramsden, D.A., Nussenzweig, A. Mechanisms driving chromosomal translocations: lost in time and space. Oncogene 40, 4263–4270 (2021). https://doi.org/10.1038/s41388-021-01856-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41388-021-01856-9

This article is cited by

Search

Advanced search

Quick links