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Genome-wide Translocation Sequencing Reveals Mechanisms of Chromosome Breaks and Rearrangements in B Cells

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Chiarle, Roberto, Zhang, Yu, Frock, Richard L., Lewis, Susanna M., Molinie, Benoit, Ho, Yu-Jui, Myers, Darienne R., Choi, Vivian W., Compagno, Mara, Malkin, Daniel J., Neuberg, Donna, Monti, Stefano, Giallourakis, Cosmas C., Gostissa, Monica, Alt, Frederick W.·2011·Cell
DOI 10.1016/j.cell.2011.07.049
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Abstract

SUMMARY While chromosomal translocations are common pathogenetic events in cancer, mechanisms that promote them are poorly understood. To elucidate translocation mechanisms in mammalian cells, we developed high throughput, genome-wide translocation sequencing (HTGTS). We employed HTGTS to identify tens of thousands of independent translocation junctions involving fixed I-SceI meganuclease-generated DNA double strand breaks (DSBs) within the c-myc oncogene or IgH locus of B lymphocytes induced for Activation Induced-cytidine Deaminase (AID)-dependent IgH class-switching. DSBs translocated very widely across the genome, but were preferentially targeted to transcribed chromosomal regions and also to numerous AID-dependent and AID-independent hotspots, with the latter being comprised mainly of cryptic genomic I-SceI targets. Comparison of translocation junctions with genome-wide nuclear run-ons revealed a marked association between transcription start sites and translocation targeting. The majority of translocation junctions were formed via end-joining with short micro-homologies. We discuss implications of our findings for diverse fields including gene therapy and cancer genomics.

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Research works printed but not linked: 48

  1. Aguilera, 2002, The connection between transcription and genomic instability, EMBO J., 21, 195, 10.1093/emboj/21.3.195 · DOI · Paper page
  2. Arnould, 2011, The I-CreI meganuclease and its engineered derivatives: applications from cell modification to gene therapy, Protein Eng. Des. Sel., 24, 27, 10.1093/protein/gzq083 · DOI
  3. Chaudhuri, 2007, Evolution of the immunoglobulin heavy chain class switch recombination mechanism, Adv. Immunol., 94, 157, 10.1016/S0065-2776(06)94006-1 · DOI · Paper page
  4. Christian, 2010, Targeting DNA double-strand breaks with TAL effector nucleases, Genetics, 186, 757, 10.1534/genetics.110.120717 · DOI · Paper page
  5. Core, 2008, Nascent RNA sequencing reveals widespread pausing and divergent initiation at human promoters, Science, 322, 1845, 10.1126/science.1162228 · DOI · Paper page
  6. Dimitrova, 2008, 53BP1 promotes non-homologous end joining of telomeres by increasing chromatin mobility, Nature, 456, 524, 10.1038/nature07433 · DOI · Paper page
  7. Dudley, 2002, Internal IgH class switch region deletions are position-independent and enhanced by AID expression, Proc. Natl. Acad. Sci. USA, 99, 9984, 10.1073/pnas.152333499 · DOI
  8. Ferguson, 2000, The nonhomologous end-joining pathway of DNA repair is required for genomic stability and the suppression of translocations, Proc. Natl. Acad. Sci. USA, 97, 6630, 10.1073/pnas.110152897 · DOI · Paper page
  9. Franco, 2006, H2AX prevents DNA breaks from progressing to chromosome breaks and translocations, Mol. Cell, 21, 201, 10.1016/j.molcel.2006.01.005 · DOI · Paper page
  10. Giallourakis, 2010, Elements between the IgH variable (V) and diversity (D) clusters influence antisense transcription and lineage-specific V(D)J recombination, Proc. Natl. Acad. Sci. USA, 107, 22207, 10.1073/pnas.1015954107 · DOI
  11. Gómez-González, 2007, Activation-induced cytidine deaminase action is strongly stimulated by mutations of the THO complex, Proc. Natl. Acad. Sci. USA, 104, 8409, 10.1073/pnas.0702836104 · DOI
  12. Gostissa, 2011, Mechanisms that promote and suppress chromosomal translocations in lymphocytes, Annu. Rev. Immunol., 29, 319, 10.1146/annurev-immunol-031210-101329 · DOI
  13. Gostissa, 2009, Chromosomal location targets different MYC family gene members for oncogenic translocations, Proc. Natl. Acad. Sci. USA, 106, 2265, 10.1073/pnas.0812763106 · DOI
  14. Haffner, 2011, Transcription-induced DNA double strand breaks: both an oncogenic force and potential therapeutic target?, Clin. Cancer Res., 17, 3858, 10.1158/1078-0432.CCR-10-2044 · DOI
  15. Händel, 2011, Zinc-finger nuclease based genome surgery: it's all about specificity, Curr. Gene Ther., 11, 28, 10.2174/156652311794520120 · DOI
  16. Jasin, 1996, Genetic manipulation of genomes with rare-cutting endonucleases, Trends Genet., 12, 224, 10.1016/0168-9525(96)10019-6 · DOI · Paper page
  17. Kovalchuk, 2007, AID-deficient Bcl-xL transgenic mice develop delayed atypical plasma cell tumors with unusual Ig/Myc chromosomal rearrangements, J. Exp. Med., 204, 2989, 10.1084/jem.20070882 · DOI
  18. Küppers, 2001, Mechanisms of chromosomal translocations in B cell lymphomas, Oncogene, 20, 5580, 10.1038/sj.onc.1204640 · DOI · Paper page
  19. Li, 2006, Cotranscriptional processes and their influence on genome stability, Genes Dev., 20, 1838, 10.1101/gad.1438306 · DOI · Paper page
  20. Lieberman-Aiden, 2009, Comprehensive mapping of long-range interactions reveals folding principles of the human genome, Science, 326, 289, 10.1126/science.1181369 · DOI · Paper page
  21. Lin, 2009, Nuclear receptor-induced chromosomal proximity and DNA breaks underlie specific translocations in cancer, Cell, 139, 1069, 10.1016/j.cell.2009.11.030 · DOI · Paper page
  22. Liu, 2009, Balancing AID and DNA repair during somatic hypermutation, Trends Immunol., 30, 173, 10.1016/j.it.2009.01.007 · DOI · Paper page
  23. Liu, 2008, Two levels of protection for the B cell genome during somatic hypermutation, Nature, 451, 841, 10.1038/nature06547 · DOI · Paper page
  24. Mahowald, 2009, Aberrantly resolved RAG-mediated DNA breaks in Atm-deficient lymphocytes target chromosomal breakpoints in cis, Proc. Natl. Acad. Sci. USA, 106, 18339, 10.1073/pnas.0902545106 · DOI
  25. Meaburn, 2007, Spatial genome organization in the formation of chromosomal translocations, Semin. Cancer Biol., 17, 80, 10.1016/j.semcancer.2006.10.008 · DOI · Paper page
  26. Muramatsu, 2000, Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme, Cell, 102, 553, 10.1016/S0092-8674(00)00078-7 · DOI · Paper page
  27. Nussenzweig, 2010, Origin of chromosomal translocations in lymphoid cancer, Cell, 141, 27, 10.1016/j.cell.2010.03.016 · DOI · Paper page
  28. Pasqualucci, 2001, Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas, Nature, 412, 341, 10.1038/35085588 · DOI · Paper page
  29. Pavri, 2011, AID Targeting in Antibody Diversity, Adv. Immunol., 110, 1, 10.1016/B978-0-12-387663-8.00005-3 · DOI
  30. Quinlan, 2010, Genome-wide mapping and assembly of structural variant breakpoints in the mouse genome, Genome Res., 20, 623, 10.1101/gr.102970.109 · DOI · Paper page
  31. Ramiro, 2006, Role of genomic instability and p53 in AID-induced c-myc-Igh translocations, Nature, 440, 105, 10.1038/nature04495 · DOI · Paper page
  32. Reynaud, 2005, Interallelic class switch recombination contributes significantly to class switching in mouse B cells, J. Immunol., 174, 6176, 10.4049/jimmunol.174.10.6176 · DOI
  33. Robbiani, 2008, AID is required for the chromosomal breaks in c-myc that lead to c-myc/IgH translocations, Cell, 135, 1028, 10.1016/j.cell.2008.09.062 · DOI · Paper page
  34. Shaffer, 2006, Breaking the rules of cancer, Nat. Med., 12, 14, 10.1038/nm0106-14 · DOI
  35. Siebert, 1995, An improved PCR method for walking in uncloned genomic DNA, Nucleic Acids Res., 23, 1087, 10.1093/nar/23.6.1087 · DOI · Paper page
  36. Simsek, 2010, Alternative end-joining is suppressed by the canonical NHEJ component Xrcc4-ligase IV during chromosomal translocation formation, Nat. Struct. Mol. Biol., 17, 410, 10.1038/nsmb.1773 · DOI · Paper page
  37. Stratton, 2009, The cancer genome, Nature, 458, 719, 10.1038/nature07943 · DOI · Paper page
  38. Unniraman, 2004, Identification of an AID-independent pathway for chromosomal translocations between the Igh switch region and Myc, Nat. Immunol., 5, 1117, 10.1038/ni1127 · DOI
  39. Wang, 2009, Mechanisms promoting translocations in editing and switching peripheral B cells, Nature, 460, 231, 10.1038/nature08159 · DOI
  40. Yamane, 2011, Deep-sequencing identification of the genomic targets of the cytidine deaminase AID and its cofactor RPA in B lymphocytes, Nat. Immunol., 12, 62, 10.1038/ni.1964 · DOI · Paper page
  41. Yan, 2007, IgH class switching and translocations use a robust non-classical end-joining pathway, Nature, 449, 478, 10.1038/nature06020 · DOI · Paper page
  42. Yu, 2003, R-loops at immunoglobulin class switch regions in the chromosomes of stimulated B cells, Nat. Immunol., 4, 442, 10.1038/ni919 · DOI · Paper page
  43. Zarrin, 2007, Antibody class switching mediated by yeast endonuclease-generated DNA breaks, Science, 315, 377, 10.1126/science.1136386 · DOI
  44. Zhang, 2010, The role of mechanistic factors in promoting chromosomal translocations found in lymphoid and other cancers, Adv. Immunol., 106, 93, 10.1016/S0065-2776(10)06004-9 · DOI
  45. Johnson, M., Zaretskaya, I., Raytselis, Y., Merezhuk, Y., McGinnis, S., and Madden, T.L. (2008). NCBI BLAST: a better web interface. Nucleic Acids Res. 36, W5-W9. · DOI · Paper page
  46. Krzywinski, M., Schein, J., Birol, I., Connors, J., Gascoyne, R., Horsman, D., Jones, S.J., and Marra, M.A. (2009). Circos: An information aesthetic for comparative genomics. Genome Res. 19, 1639–1645. · DOI · Paper page
  47. Petek, L.M., Russell, D.W., and Miller, D.G. (2010). Frequent endonuclease cleavage at off-target locations in vivo. Mol. Ther. 18, 983–986. · DOI
  48. Sasaki, Y., Derudder, E., Hobeika, E., Pelanda, R., Reth, M., Rajewsky, K., and Schmidt-Supprian, M. (2006). Canonical NF-kappaB activity, dispensable for B cell development, replaces BAFF-receptor signals and promotes B cell proliferation upon activation. Immunity 24, 729–739. · DOI · Paper page

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Metadata

Authors
Chiarle, R., Zhang, Y., Frock, R. L., Lewis, S. M., Molinie, B., Ho, Y.-J., Myers, D. R., Choi, V. W., Compagno, M., Malkin, D. J., Neuberg, D., Monti, S., Giallourakis, C. C., Gostissa, M., & Alt, F. W.
Venue
Cell
Publisher
Elsevier BV
Published
2011-09
Volume
147
Issue
1
Pages
107-119
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2011.07.049
OpenAlex
W2097627856
Cited by
474
References
4
FWCI
16.69
Type
journal article
Language
en
Open access
bronze
Licence

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CoChat. (2026). Citation check: Genome-wide Translocation Sequencing Reveals Mechanisms of Chromosome Breaks and Rearrangements in B Cells. https://app.cochat.ai/papers/10.1016/j.cell.2011.07.049
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Chiarle, R., Zhang, Y., Frock, R. L., Lewis, S. M., Molinie, B., Ho, Y.-J., Myers, D. R., Choi, V. W., Compagno, M., Malkin, D. J., Neuberg, D., Monti, S., Giallourakis, C. C., Gostissa, M., & Alt, F. W. (2011). Genome-wide Translocation Sequencing Reveals Mechanisms of Chromosome Breaks and Rearrangements in B Cells. Cell. https://doi.org/10.1016/j.cell.2011.07.049

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