Skip to main content
SpringerLink
Log in

Mechanisms and impacts of chromosomal translocations in cancers

  • Review
  • Published:
Frontiers of Medicine Aims and scope Submit manuscript

Abstract

Chromosomal aberrations have been associated with cancer development since their discovery more than a hundred years ago. Chromosomal translocations, a type of particular structural changes involving heterologous chromosomes, have made a critical impact on diagnosis, prognosis and treatment of cancers. For example, the discovery of translocation between chromosomes 9 and 22 and the subsequent success of targeting the fusion product BCR-ABL transformed the therapy for chronic myelogenous leukemia. In the past few decades, tremendous progress has been achieved towards elucidating the mechanism causing chromosomal translocations. This review focuses on the basic mechanisms underlying the generation of chromosomal translocations. In particular, the contribution of frequency of DNA double strand breaks and spatial proximity of translocating loci is discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Balmain A. Cancer genetics: from Boveri and Mendel to microarrays. Nat Rev Cancer 2001; 1(1): 77–82

    Article  PubMed  CAS  Google Scholar 

  2. Rowley JD. Chromosome translocations: dangerous liaisons revisited. Nat Rev Cancer 2001; 1(3): 245–250

    Article  PubMed  CAS  Google Scholar 

  3. Levan A. Some current problems of cancer cytogenetics. Hereditas 1967; 57(3): 343–355

    Article  PubMed  CAS  Google Scholar 

  4. Mitelman F, Johansson B, Mertens F. The impact of translocations and gene fusions on cancer causation. Nat Rev Cancer 2007; 7(4): 233–245

    Article  PubMed  CAS  Google Scholar 

  5. Stratton MR. Exploring the genomes of cancer cells: progress and promise. Science 2011; 331(6024): 1553–1558

    Article  PubMed  CAS  Google Scholar 

  6. Stratton MR, Campbell PJ, Futreal PA. The cancer genome. Nature 2009; 458(7239): 719–724

    Article  PubMed  CAS  Google Scholar 

  7. Negrini S, Gorgoulis VG, Halazonetis TD. Genomic instability—an evolving hallmark of cancer. Nat Rev Mol Cell Biol 2010; 11(3): 220–228

    Article  PubMed  CAS  Google Scholar 

  8. Pleasance ED, Cheetham RK, Stephens PJ, McBride DJ, Humphray SJ, Greenman CD, Varela I, Lin ML, Ordóñez GR, Bignell GR, Ye K, Alipaz J, Bauer MJ, Beare D, Butler A, Carter RJ, Chen L, Cox AJ, Edkins S, Kokko-Gonzales PI, Gormley NA, Grocock RJ, Haudenschild CD, Hims MM, James T, Jia M, Kingsbury Z, Leroy C, Marshall J, Menzies A, Mudie LJ, Ning Z, Royce T, Schulz-Trieglaff OB, Spiridou A, Stebbings LA, Szajkowski L, Teague J, Williamson D, Chin L, Ross MT, Campbell PJ, Bentley DR, Futreal PA, Stratton MR. A comprehensive catalogue of somatic mutations from a human cancer genome. Nature 2010; 463(7278): 191–196

    Article  PubMed  CAS  Google Scholar 

  9. Pleasance ED, Stephens PJ, O’Meara S, McBride DJ, Meynert A, Jones D, Lin ML, Beare D, Lau KW, Greenman C, Varela I, Nik-Zainal S, Davies HR, Ordoñez GR, Mudie LJ, Latimer C, Edkins S, Stebbings L, Chen L, Jia M, Leroy C, Marshall J, Menzies A, Butler A, Teague JW, Mangion J, Sun YA, McLaughlin SF, Peckham HE, Tsung EF, Costa GL, Lee CC, Minna JD, Gazdar A, Birney E, Rhodes MD, McKernan KJ, Stratton MR, Futreal PA, Campbell PJ. A small-cell lung cancer genome with complex signatures of tobacco exposure. Nature 2010; 463(7278): 184–190

    Article  PubMed  CAS  Google Scholar 

  10. Stephens PJ, McBride DJ, Lin ML, Varela I, Pleasance ED, Simpson JT, Stebbings LA, Leroy C, Edkins S, Mudie LJ, Greenman CD, Jia M, Latimer C, Teague JW, Lau KW, Burton J, Quail MA, Swerdlow H, Churcher C, Natrajan R, Sieuwerts AM, Martens JW, Silver DP, Langerød A, Russnes HE, Foekens JA, Reis-Filho JS, van’t Veer L, Richardson AL, Børresen-Dale AL, Campbell PJ, Futreal PA, Stratton MR. Complex landscapes of somatic rearrangement in human breast cancer genomes. Nature 2009; 462(7276): 1005–1010

    Article  PubMed  CAS  Google Scholar 

  11. Nowell PC, Hungerford DA. Chromosome studies on normal and leukemic human leukocytes. J Natl Cancer Inst 1960; 25: 85–109

    PubMed  CAS  Google Scholar 

  12. Nowell PC, Rowley JD, Knudson AG Jr. Cancer genetics, cytogenetics—defining the enemy within. Nat Med 1998; 4(10): 1107–1111

    Article  PubMed  CAS  Google Scholar 

  13. Rowley JD. Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 1973; 243(5405): 290–293

    Article  PubMed  CAS  Google Scholar 

  14. Rowley JD. Identificaton of a translocation with quinacrine fluorescence in a patient with acute leukemia. Ann Genet 1973; 16(2): 109–112

    PubMed  CAS  Google Scholar 

  15. Morris DS, Tomlins SA, Montie JE, Chinnaiyan AM. The discovery and application of gene fusions in prostate cancer. BJU Int 2008; 102(3): 276–282

    Article  PubMed  CAS  Google Scholar 

  16. Mano H. Non-solid oncogenes in solid tumors: EML4-ALK fusion genes in lung cancer. Cancer Sci 2008; 99(12): 2349–2355

    Article  PubMed  CAS  Google Scholar 

  17. Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, Fujiwara S, Watanabe H, Kurashina K, Hatanaka H, Bando M, Ohno S, Ishikawa Y, Aburatani H, Niki T, Sohara Y, Sugiyama Y, Mano H. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 2007; 448(7153): 561–566

    Article  PubMed  CAS  Google Scholar 

  18. Groffen J, Stephenson JR, Heisterkamp N, de Klein A, Bartram CR, Grosveld G. Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22. Cell 1984; 36(1): 93–99

    Article  PubMed  CAS  Google Scholar 

  19. Kurzrock R, Kantarjian HM, Druker BJ, Talpaz M. Philadelphia chromosome-positive leukemias: from basic mechanisms to molecular therapeutics. Ann Intern Med 2003; 138(10): 819–830

    PubMed  CAS  Google Scholar 

  20. Shtivelman E, Lifshitz B, Gale RP, Canaani E. Fused transcript of abl and bcr genes in chronic myelogenous leukaemia. Nature 1985; 315(6020): 550–554

    Article  PubMed  CAS  Google Scholar 

  21. Foroni L, Gerrard G, Nna E, Khorashad JS, Stevens D, Swale B, Milojkovic D, Reid A, Goldman J, Marin D. Technical aspects and clinical applications of measuring BCR-ABL1 transcripts number in chronic myeloid leukemia. Am J Hematol 2009; 84(8): 517–522

    Article  PubMed  CAS  Google Scholar 

  22. Szczylik C, Skorski T, Nicolaides NC, Manzella L, Malaguarnera L, Venturelli D, Gewirtz AM, Calabretta B. Selective inhibition of leukemia cell proliferation by BCR-ABL antisense oligodeoxynucleotides. Science 1991; 253(5019): 562–565

    Article  PubMed  CAS  Google Scholar 

  23. Van Etten RA, Jackson P, Baltimore D. The mouse type IV c-abl gene product is a nuclear protein, and activation of transforming ability is associated with cytoplasmic localization. Cell 1989; 58(4): 669–678

    Article  PubMed  Google Scholar 

  24. Konopka JB, Watanabe SM, Witte ON. An alteration of the human c-abl protein in K562 leukemia cells unmasks associated tyrosine kinase activity. Cell 1984; 37(3): 1035–1042

    Article  PubMed  CAS  Google Scholar 

  25. Barilá D, Superti-Furga G. An intramolecular SH3-domain interaction regulates c-Abl activity. Nat Genet 1998; 18(3): 280–282

    Article  PubMed  Google Scholar 

  26. Franz WM, Berger P, Wang JY. Deletion of an N-terminal regulatory domain of the c-abl tyrosine kinase activates its oncogenic potential. EMBO J 1989; 8(1): 137–147

    PubMed  CAS  Google Scholar 

  27. Jackson P, Baltimore D. N-terminal mutations activate the leukemogenic potential of the myristoylated form of c-abl. EMBO J 1989; 8(2): 449–456

    PubMed  CAS  Google Scholar 

  28. Mayer BJ, Baltimore D. Mutagenic analysis of the roles of SH2 and SH3 domains in regulation of the Abl tyrosine kinase. Mol Cell Biol 1994; 14(5): 2883–2894

    PubMed  CAS  Google Scholar 

  29. Pendergast AM, Muller AJ, Havlik MH, Clark R, McCormick F, Witte ON. Evidence for regulation of the human ABL tyrosine kinase by a cellular inhibitor. Proc Natl Acad Sci USA 1991; 88(13): 5927–5931

    Article  PubMed  CAS  Google Scholar 

  30. Deininger M, Buchdunger E, Druker BJ. The development of imatinib as a therapeutic agent for chronic myeloid leukemia. Blood 2005; 105(7): 2640–2653

    Article  PubMed  CAS  Google Scholar 

  31. Berger R, Chen SJ, Chen Z. Philadelphia-positive acute leukemia. Cytogenetic and molecular aspects. Cancer Genet Cytogenet 1990; 44(2): 143–152

    Article  PubMed  CAS  Google Scholar 

  32. Druker BJ, Sawyers CL, Kantarjian H, Resta DJ, Reese SF, Ford JM, Capdeville R, Talpaz M. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med 2001; 344(14): 1038–1042

    Article  PubMed  CAS  Google Scholar 

  33. Dalla-Favera R, Bregni M, Erikson J, Patterson D, Gallo RC, Croce CM. Human c-myc onc gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells. Proc Natl Acad Sci USA 1982; 79(24): 7824–7827

    Article  PubMed  CAS  Google Scholar 

  34. Zech L, Haglund U, Nilsson K, Klein G. Characteristic chromosomal abnormalities in biopsies and lymphoid-cell lines from patients with Burkitt and non-Burkitt lymphomas. Int J Cancer 1976; 17(1): 47–56

    Article  PubMed  CAS  Google Scholar 

  35. Taub R, Kirsch I, Morton C, Lenoir G, Swan D, Tronick S, Aaronson S, Leder P. Translocation of the c-myc gene into the immunoglobulin heavy chain locus in human Burkitt lymphoma and murine plasmacytoma cells. Proc Natl Acad Sci USA 1982; 79(24): 7837–7841

    Article  PubMed  CAS  Google Scholar 

  36. Küppers R, Dalla-Favera R. Mechanisms of chromosomal translocations in B cell lymphomas. Oncogene 2001; 20(40): 5580–5594

    Article  PubMed  Google Scholar 

  37. ar-Rushdi A, Nishikura K, Erikson J, Watt R, Rovera G, Croce CM. Differential expression of the translocated and the untranslocated c-myc oncogene in Burkitt lymphoma. Science 1983; 222(4622): 390–393

    Article  PubMed  CAS  Google Scholar 

  38. Kanungo A, Medeiros LJ, Abruzzo LV, Lin P. Lymphoid neoplasms associated with concurrent t(14;18) and 8q24/c-MYC translocation generally have a poor prognosis. Mod Pathol 2006; 19(1): 25–33

    Article  PubMed  CAS  Google Scholar 

  39. Adams JM, Harris AW, Pinkert CA, Corcoran LM, Alexander WS, Cory S, Palmiter RD, Brinster RL. The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice. Nature 1985; 318(6046): 533–538

    Article  PubMed  CAS  Google Scholar 

  40. Janz S. Myc translocations in B cell and plasma cell neoplasms. DNA Repair (Amst) 2006; 5(9–10): 1213–1224

    Article  CAS  Google Scholar 

  41. Wang JH, Alt FW, Gostissa M, Datta A, Murphy M, Alimzhanov MB, Coakley KM, Rajewsky K, Manis JP, Yan CT. Oncogenic transformation in the absence of Xrcc4 targets peripheral B cells that have undergone editing and switching. J Exp Med 2008; 205(13): 3079–3090

    Article  PubMed  CAS  Google Scholar 

  42. Boxer LM, Dang CV. Translocations involving c-myc and c-myc function. Oncogene 2001; 20(40): 5595–5610

    Article  PubMed  CAS  Google Scholar 

  43. Truffinet V, Pinaud E, Cogné N, Petit B, Guglielmi L, Cogné M, Denizot Y. The 3′ IgH locus control region is sufficient to deregulate a c-myc transgene and promote mature B cell malignancies with a predominant Burkitt-like phenotype. J Immunol 2007; 179(9): 6033–6042

    PubMed  CAS  Google Scholar 

  44. Wang J, Boxer LM. Regulatory elements in the immunoglobulin heavy chain gene 3′-enhancers induce c-myc deregulation and lymphomagenesis in murine B cells. J Biol Chem 2005; 280(13): 12766–12773

    Article  PubMed  CAS  Google Scholar 

  45. Yan Y, Park SS, Janz S, Eckhardt LA. In a model of immunoglobulin heavy-chain (IGH)/MYC translocation, the Igh 3′ regulatory region induces MYC expression at the immature stage of B cell development. Genes Chromosomes Cancer 2007; 46(10): 950–959

    Article  PubMed  CAS  Google Scholar 

  46. Gostissa M, Yan CT, Bianco JM, Cogné M, Pinaud E, Alt FW. Long-range oncogenic activation of Igh-c-myc translocations by the Igh 3′ regulatory region. Nature 2009; 462(7274): 803–807

    Article  PubMed  CAS  Google Scholar 

  47. Miyoshi H, Shimizu K, Kozu T, Maseki N, Kaneko Y, Ohki M. t (8;21) breakpoints on chromosome 21 in acute myeloid leukemia are clustered within a limited region of a single gene, AML1. Proc Natl Acad Sci USA 1991; 88(23): 10431–10434

    Article  PubMed  CAS  Google Scholar 

  48. Tsujimoto Y, Finger LR, Yunis J, Nowell PC, Croce CM. Cloning of the chromosome breakpoint of neoplastic B cells with the t (14;18) chromosome translocation. Science 1984; 226(4678): 1097–1099

    Article  PubMed  CAS  Google Scholar 

  49. Vaux DL, Cory S, Adams JM. Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature 1988; 335(6189): 440–442

    Article  PubMed  CAS  Google Scholar 

  50. Gostissa M, Alt FW, Chiarle R. Mechanisms that promote and suppress chromosomal translocations in lymphocytes. Annu Rev Immunol 2011; 29(1): 319–350

    Article  PubMed  CAS  Google Scholar 

  51. Zhang Y, Gostissa M, Hildebrand DG, Becker MS, Boboila C, Chiarle R, Lewis S, Alt FW. The role of mechanistic factors in promoting chromosomal translocations found in lymphoid and other cancers. Adv Immunol 2010; 106: 93–133

    Article  PubMed  CAS  Google Scholar 

  52. Lieber MR, Yu K, Raghavan SC. Roles of nonhomologous DNA end joining, V(D)J recombination, and class switch recombination in chromosomal translocations. DNA Repair (Amst) 2006; 5(9–10): 1234–1245

    Article  CAS  Google Scholar 

  53. Marculescu R, Vanura K, Montpellier B, Roulland S, Le T, Navarro JM, Jäger U, McBlane F, Nadel B. Recombinase, chromosomal translocations and lymphoid neoplasia: targeting mistakes and repair failures. DNA Repair (Amst) 2006; 5(9–10): 1246–1258

    Article  CAS  Google Scholar 

  54. Tsai AG, Lieber MR. Mechanisms of chromosomal rearrangement in the human genome. BMC Genomics 2010; 11(Suppl 1): S1

    Article  PubMed  CAS  Google Scholar 

  55. Schatz DG, Swanson PC. V(D)J recombination: mechanisms of initiation. Annu Rev Genet 2011; 45(1): 167–202

    Article  PubMed  CAS  Google Scholar 

  56. Gorman JR, Alt FW. Regulation of immunoglobulin light chain isotype expression. Adv Immunol 1998; 69: 113–181

    Article  PubMed  CAS  Google Scholar 

  57. Jung D, Giallourakis C, Mostoslavsky R, Alt FW. Mechanism and control of V(D)J recombination at the immunoglobulin heavy chain locus. Annu Rev Immunol 2006; 24(1): 541–570

    Article  PubMed  CAS  Google Scholar 

  58. Bassing CH, Swat W, Alt FW. The mechanism and regulation of chromosomal V(D)J recombination. Cell 2002; 109(2 Suppl): S45–S55

    Article  PubMed  CAS  Google Scholar 

  59. Chaudhuri J, Basu U, Zarrin A, Yan C, Franco S, Perlot T, Vuong B, Wang J, Phan RT, Datta A, Manis J, Alt FW. Evolution of the immunoglobulin heavy chain class switch recombination mechanism. Adv Immunol 2007; 94: 157–214

    Article  PubMed  CAS  Google Scholar 

  60. Gao Y, Sun Y, Frank KM, Dikkes P, Fujiwara Y, Seidl KJ, Sekiguchi JM, Rathbun GA, Swat W, Wang J, Bronson RT, Malynn BA, Bryans M, Zhu C, Chaudhuri J, Davidson L, Ferrini R, Stamato T, Orkin SH, Greenberg ME, Alt FW. A critical role for DNA end-joining proteins in both lymphogenesis and neurogenesis. Cell 1998; 95(7): 891–902

    Article  PubMed  CAS  Google Scholar 

  61. Yan CT, Boboila C, Souza EK, Franco S, Hickernell TR, Murphy M, Gumaste S, Geyer M, Zarrin AA, Manis JP, Rajewsky K, Alt FW. IgH class switching and translocations use a robust nonclassical end-joining pathway. Nature 2007; 449(7161): 478–482

    Article  PubMed  CAS  Google Scholar 

  62. Lieber MR. The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu Rev Biochem 2010; 79(1): 181–211

    Article  PubMed  CAS  Google Scholar 

  63. Nambiar M, Raghavan SC. How does DNA break during chromosomal translocations? Nucleic Acids Res 2011; 39(14): 5813–5825

    Article  PubMed  CAS  Google Scholar 

  64. Lewis SM, Agard E, Suh S, Czyzyk L. Cryptic signals and the fidelity of V(D)J joining. Mol Cell Biol 1997; 17(6): 3125–3136

    PubMed  CAS  Google Scholar 

  65. Marculescu R, Le T, Simon P, Jaeger U, Nadel BV. V(D)Jmediated translocations in lymphoid neoplasms: a functional assessment of genomic instability by cryptic sites. J Exp Med 2002; 195(1): 85–98

    Article  PubMed  CAS  Google Scholar 

  66. Raghavan SC, Kirsch IR, Lieber MR. Analysis of the V(D)J recombination efficiency at lymphoid chromosomal translocation breakpoints. J Biol Chem 2001; 276(31): 29126–29133

    Article  PubMed  CAS  Google Scholar 

  67. Nambiar M, Goldsmith G, Moorthy BT, Lieber MR, Joshi MV, Choudhary B, Hosur RV, Raghavan SC. Formation of a G-quadruplex at the BCL2 major breakpoint region of the t(14;18) translocation in follicular lymphoma. Nucleic Acids Res 2011; 39(3): 936–948

    Article  PubMed  CAS  Google Scholar 

  68. Raghavan SC, Swanson PC, Wu X, Hsieh CL, Lieber MR. A non-B-DNA structure at the Bcl-2 major breakpoint region is cleaved by the RAG complex. Nature 2004; 428(6978): 88–93

    Article  PubMed  CAS  Google Scholar 

  69. Küppers R. Mechanisms of B-cell lymphoma pathogenesis. Nat Rev Cancer 2005; 5(4): 251–262

    Article  PubMed  CAS  Google Scholar 

  70. Tsai AG, Lu H, Raghavan SC, Muschen M, Hsieh CL, Lieber MR. Human chromosomal translocations at CpG sites and a theoretical basis for their lineage and stage specificity. Cell 2008; 135(6): 1130–1142

    Article  PubMed  CAS  Google Scholar 

  71. Gazumyan A, Bothmer A, Klein IA, Nussenzweig MC, McBride KM. Activation-induced cytidine deaminase in antibody diversification and chromosome translocation. Adv Cancer Res 2012; 113: 167–190

    Article  PubMed  Google Scholar 

  72. Kovalchuk AL, duBois W, Mushinski E, McNeil NE, Hirt C, Qi CF, Li Z, Janz S, Honjo T, Muramatsu M, Ried T, Behrens T, Potter M. AID-deficient Bcl-xL transgenic mice develop delayed atypical plasma cell tumors with unusual Ig/Myc chromosomal rearrangements. J Exp Med 2007; 204(12): 2989–3001

    Article  PubMed  CAS  Google Scholar 

  73. Ramiro AR, Jankovic M, Eisenreich T, Difilippantonio S, Chen-Kiang S, Muramatsu M, Honjo T, Nussenzweig A, Nussenzweig MC. AID is required for c-myc/IgH chromosome translocations in vivo. Cell 2004; 118(4): 431–438

    Article  PubMed  CAS  Google Scholar 

  74. Robbiani DF, Bothmer A, Callen E, Reina-San-Martin B, Dorsett Y, Difilippantonio S, Bolland DJ, Chen HT, Corcoran AE, Nussenzweig A, Nussenzweig MC. AID is required for the chromosomal breaks in c-myc that lead to c-myc/IgH translocations. Cell 2008; 135(6): 1028–1038

    Article  PubMed  CAS  Google Scholar 

  75. Jäger U, Böcskör S, Le T, Mitterbauer G, Bolz I, Chott A, Kneba M, Mannhalter C, Nadel B. Follicular lymphomas’ BCL-2/IgH junctions contain templated nucleotide insertions: novel insights into the mechanism of t(14;18) translocation. Blood 2000; 95(11): 3520–3529

    PubMed  Google Scholar 

  76. Wang JH, Gostissa M, Yan CT, Goff P, Hickernell T, Hansen E, Difilippantonio S, Wesemann DR, Zarrin AA, Rajewsky K, Nussenzweig A, Alt FW. Mechanisms promoting translocations in editing and switching peripheral B cells. Nature 2009; 460(7252): 231–236

    Article  PubMed  CAS  Google Scholar 

  77. Bassing CH, Alt FW. The cellular response to general and programmed DNA double strand breaks. DNA Repair (Amst) 2004; 3(8–9): 781–796

    Article  CAS  Google Scholar 

  78. Savage JR. Reflections and meditations upon complex chromosomal exchanges. Mutat Res 2002; 512(2–3): 93–109

    PubMed  CAS  Google Scholar 

  79. Richardson C, Jasin M. Frequent chromosomal translocations induced by DNA double-strand breaks. Nature 2000; 405(6787): 697–700

    Article  PubMed  CAS  Google Scholar 

  80. Bellaiche Y, Mogila V, Perrimon N. I-SceI endonuclease, a new tool for studying DNA double-strand break repair mechanisms in Drosophila. Genetics 1999; 152(3): 1037–1044

    PubMed  CAS  Google Scholar 

  81. Jasin M. Genetic manipulation of genomes with rare-cutting endonucleases. Trends Genet 1996; 12(6): 224–228

    Article  PubMed  CAS  Google Scholar 

  82. Zarrin AA, Del Vecchio C, Tseng E, Gleason M, Zarin P, Tian M, Alt FW. Antibody class switching mediated by yeast endonuclease-generated DNA breaks. Science 2007; 315(5810): 377–381

    Article  PubMed  CAS  Google Scholar 

  83. Chiarle R, Zhang Y, Frock RL, Lewis SM, Molinie B, Ho YJ, Myers DR, Choi VW, Compagno M, Malkin DJ, Neuberg D, Monti S, Giallourakis CC, Gostissa M, Alt FW. Genome-wide translocation sequencing reveals mechanisms of chromosome breaks and rearrangements in B cells. Cell 2011; 147(1): 107–119

    Article  PubMed  CAS  Google Scholar 

  84. Klein IA, Resch W, Jankovic M, Oliveira T, Yamane A, Nakahashi H, Di Virgilio M, Bothmer A, Nussenzweig A, Robbiani DF, Casellas R, Nussenzweig MC. Translocation-capture sequencing reveals the extent and nature of chromosomal rearrangements in B lymphocytes. Cell 2011; 147(1): 95–106

    Article  PubMed  CAS  Google Scholar 

  85. Lin C, Yang L, Tanasa B, Hutt K, Ju BG, Ohgi K, Zhang J, Rose DW, Fu XD, Glass CK, Rosenfeld MG. Nuclear receptor-induced chromosomal proximity and DNA breaks underlie specific translocations in cancer. Cell 2009; 139(6): 1069–1083

    Article  PubMed  CAS  Google Scholar 

  86. Mahowald GK, Baron JM, Mahowald MA, Kulkarni S, Bredemeyer AL, Bassing CH, Sleckman BP. Aberrantly resolved RAGmediated DNA breaks in Atm-deficient lymphocytes target chromosomal breakpoints in cis. Proc Natl Acad Sci USA 2009; 106(43): 18339–18344

    Article  PubMed  CAS  Google Scholar 

  87. Weinstock DM, Brunet E, Jasin M. Induction of chromosomal translocations in mouse and human cells using site-specific endonucleases. J Natl Cancer Inst Monogr 2008; 39: 20–24

    Article  PubMed  CAS  Google Scholar 

  88. Stoddard BL. Homing endonuclease structure and function. Q Rev Biophys 2005; 38(1): 49–95

    Article  PubMed  CAS  Google Scholar 

  89. Savage JR. Proximity matters. Science 2000; 290(5489): 62–63

    Article  PubMed  CAS  Google Scholar 

  90. Savage JR. A brief survey of aberration origin theories. Mutat Res 1998; 404(1–2): 139–147

    PubMed  CAS  Google Scholar 

  91. Cremer T, Cremer C. Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nat Rev Genet 2001; 2(4): 292–301

    Article  PubMed  CAS  Google Scholar 

  92. Cremer T, Cremer M. Chromosome territories. Cold Spring Harb Perspect Biol 2010; 2(3): a003889

    Article  PubMed  CAS  Google Scholar 

  93. Gilbert N, Boyle S, Fiegler H, Woodfine K, Carter NP, Bickmore WA. Chromatin architecture of the human genome: gene-rich domains are enriched in open chromatin fibers. Cell 2004; 118(5): 555–566

    Article  PubMed  CAS  Google Scholar 

  94. Lieberman-Aiden E, van Berkum NL, Williams L, Imakaev M, Ragoczy T, Telling A, Amit I, Lajoie BR, Sabo PJ, Dorschner MO, Sandstrom R, Bernstein B, Bender MA, Groudine M, Gnirke A, Stamatoyannopoulos J, Mirny LA, Lander ES, Dekker J. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 2009; 326(5950): 289–293

    Article  PubMed  CAS  Google Scholar 

  95. Aten JA, Stap J, Krawczyk PM, van Oven CH, Hoebe RA, Essers J, Kanaar R. Dynamics of DNA double-strand breaks revealed by clustering of damaged chromosome domains. Science 2004; 303(5654): 92–95

    Article  PubMed  CAS  Google Scholar 

  96. 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(5): 502–509

    Article  PubMed  CAS  Google Scholar 

  97. Miné-Hattab J, Rothstein R. Increased chromosome mobility facilitates homology search during recombination. Nat Cell Biol 2012; 14(5): 510–517

    Article  PubMed  CAS  Google Scholar 

  98. Marshall WF, Straight A, Marko JF, Swedlow J, Dernburg A, Belmont A, Murray AW, Agard DA, Sedat JW. Interphase chromosomes undergo constrained diffusional motion in living cells. Curr Biol 1997; 7(12): 930–939

    Article  PubMed  CAS  Google Scholar 

  99. Soutoglou E, Dorn JF, Sengupta K, Jasin M, Nussenzweig A, Ried T, Danuser G, Misteli T. Positional stability of single double-strand breaks in mammalian cells. Nat Cell Biol 2007; 9(6): 675–682

    Article  PubMed  CAS  Google Scholar 

  100. Meaburn KJ, Misteli T, Soutoglou E. Spatial genome organization in the formation of chromosomal translocations. Semin Cancer Biol 2007; 17(1): 80–90

    Article  PubMed  CAS  Google Scholar 

  101. Neves H, Ramos C, da Silva MG, Parreira A, Parreira L. The nuclear topography of ABL, BCR, PML, and RARalpha genes: evidence for gene proximity in specific phases of the cell cycle and stages of hematopoietic differentiation. Blood 1999; 93(4): 1197–1207

    PubMed  CAS  Google Scholar 

  102. Osborne CS, Chakalova L, Mitchell JA, Horton A, Wood AL, Bolland DJ, Corcoran AE, Fraser P. Myc dynamically and preferentially relocates to a transcription factory occupied by Igh. PLoS Biol 2007; 5(8): e192

    Article  PubMed  CAS  Google Scholar 

  103. Roix JJ, McQueen PG, Munson PJ, Parada LA, Misteli T. Spatial proximity of translocation-prone gene loci in human lymphomas. Nat Genet 2003; 34(3): 287–291

    Article  PubMed  CAS  Google Scholar 

  104. Mani RS, Tomlins SA, Callahan K, Ghosh A, Nyati MK, Varambally S, Palanisamy N, Chinnaiyan AM. Induced chromosomal proximity and gene fusions in prostate cancer. Science 2009; 326(5957): 1230

    Article  PubMed  CAS  Google Scholar 

  105. Mathas S, Kreher S, Meaburn KJ, Jöhrens K, Lamprecht B, Assaf C, Sterry W, Kadin ME, Daibata M, Joos S, Hummel M, Stein H, Janz M, Anagnostopoulos I, Schrock E, Misteli T, Dörken B. Gene deregulation and spatial genome reorganization near breakpoints prior to formation of translocations in anaplastic large cell lymphoma. Proc Natl Acad Sci USA 2009; 106(14): 5831–5836

    Article  PubMed  CAS  Google Scholar 

  106. Zhang Y, McCord RP, Ho YJ, Lajoie BR, Hildebrand DG, Simon AC, Becker MS, Alt FW, Dekker J. Spatial organization of the mouse genome and its role in recurrent chromosomal translocations. Cell 2012; 148(5): 908–921

    Article  PubMed  CAS  Google Scholar 

  107. Hakim O, Resch W, Yamane A, Klein I, Kieffer-Kwon KR, Jankovic M, Oliveira T, Bothmer A, Voss TC, Ansarah-Sobrinho C, Mathe E, Liang G, Cobell J, Nakahashi H, Robbiani DF, Nussenzweig A, Hager GL, Nussenzweig MC, Casellas R. DNA damage defines sites of recurrent chromosomal translocations in B lymphocytes. Nature 2012; 484(7392): 69–74

    PubMed  CAS  Google Scholar 

  108. Liu P, Erez A, Nagamani SC, Dhar SU, KoŁodziejska KE, Dharmadhikari AV, Cooper ML, Wiszniewska J, Zhang F, Withers MA, Bacino CA, Campos-Acevedo LD, Delgado MR, Freedenberg D, Garnica A, Grebe TA, Hernández-Almaguer D, Immken L, Lalani SR, McLean SD, Northrup H, Scaglia F, Strathearn L, Trapane P, Kang SH, Patel A, Cheung SW, Hastings PJ, Stankiewicz P, Lupski JR, Bi W. Chromosome catastrophes involve replication mechanisms generating complex genomic rearrangements. Cell 2011; 146(6): 889–903

    Article  PubMed  CAS  Google Scholar 

  109. Rausch T, Jones DT, Zapatka M, Stütz AM, Zichner T, Weischenfeldt J, Jäger N, Remke M, Shih D, Northcott PA, Pfaff E, Tica J, Wang Q, Massimi L, Witt H, Bender S, Pleier S, Cin H, Hawkins C, Beck C, von Deimling A, Hans V, Brors B, Eils R, Scheurlen W, Blake J, Benes V, Kulozik AE, Witt O, Martin D, Zhang C, Porat R, Merino DM, Wasserman J, Jabado N, Fontebasso A, Bullinger L, Rücker FG, Döhner K, Döhner H, Koster J, Molenaar JJ, Versteeg R, Kool M, Tabori U, Malkin D, Korshunov A, Taylor MD, Lichter P, Pfister SM, Korbel JO. Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations. Cell 2012; 148(1–2): 59–71

    Article  PubMed  CAS  Google Scholar 

  110. Stephens PJ, Greenman CD, Fu B, Yang F, Bignell GR, Mudie LJ, Pleasance ED, Lau KW, Beare D, Stebbings LA, McLaren S, Lin ML, McBride DJ, Varela I, Nik-Zainal S, Leroy C, Jia M, Menzies A, Butler AP, Teague JW, Quail MA, Burton J, Swerdlow H, Carter NP, Morsberger LA, Iacobuzio-Donahue C, Follows GA, Green AR, Flanagan AM, Stratton MR, Futreal PA, Campbell PJ. Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell 2011; 144(1): 27–40

    Article  PubMed  CAS  Google Scholar 

  111. Kearney L, Horsley SW. Molecular cytogenetics in haematological malignancy: current technology and future prospects. Chromosoma 2005; 114(4): 286–294

    Article  PubMed  CAS  Google Scholar 

  112. Speicher MR, Carter NP. The new cytogenetics: blurring the boundaries with molecular biology. Nat Rev Genet 2005; 6(10): 782–792

    Article  PubMed  CAS  Google Scholar 

  113. Shuen A, Foulkes WD. Clinical implications of next-generation sequencing for cancer medicine. Curr Oncol 2010; 17(5): 39–42

    PubMed  CAS  Google Scholar 

  114. Chen Z, Chen SJ, Tong JH, Zhu YJ, Huang ME, Wang WC, Wu Y, Sun GL, Wang ZY, Larsen CJ, Berger R. The retinoic acid alpha receptor gene is frequently disrupted in its 5′ part in Chinese patients with acute promyelocytic leukemia. Leukemia 1991; 5(4): 288–292

    PubMed  CAS  Google Scholar 

  115. Chen ZX, Xue YQ, Zhang R, Tao RF, Xia XM, Li C, Wang W, Zu WY, Yao XZ, Ling BJ. A clinical and experimental study on alltrans retinoic acid-treated acute promyelocytic leukemia patients. Blood 1991; 78(6): 1413–1419

    PubMed  CAS  Google Scholar 

  116. Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhoa L, Gu LJ, Wang ZY. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood 1988; 72(2): 567–572

    PubMed  CAS  Google Scholar 

  117. Morris SW, Kirstein MN, Valentine MB, Dittmer KG, Shapiro DN, Saltman DL, Look AT. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin’s lymphoma. Science 1994; 263(5151): 1281–1284

    Article  PubMed  CAS  Google Scholar 

  118. Shiota M, Fujimoto J, Semba T, Satoh H, Yamamoto T, Mori S. Hyperphosphorylation of a novel 80 kDa protein-tyrosine kinase similar to Ltk in a human Ki-1 lymphoma cell line, AMS3. Oncogene 1994; 9(6): 1567–1574

    PubMed  CAS  Google Scholar 

  119. Chen Y, Takita J, Choi YL, Kato M, Ohira M, Sanada M, Wang L, Soda M, Kikuchi A, Igarashi T, Nakagawara A, Hayashi Y, Mano H, Ogawa S. Oncogenic mutations of ALK kinase in neuroblastoma. Nature 2008; 455(7215): 971–974

    Article  PubMed  CAS  Google Scholar 

  120. Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, Ou SH, Dezube BJ, Jänne PA, Costa DB, Varella-Garcia M, Kim WH, Lynch TJ, Fidias P, Stubbs H, Engelman JA, Sequist LV, Tan W, Gandhi L, Mino-Kenudson M, Wei GC, Shreeve SM, Ratain MJ, Settleman J, Christensen JG, Haber DA, Wilner K, Salgia R, Shapiro GI, Clark JW, Iafrate AJ. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med 2010; 363(18): 1693–1703

    Article  PubMed  CAS  Google Scholar 

  121. Solomon B, Varella-Garcia M, Camidge DR. ALK gene rearrangements: a new therapeutic target in a molecularly defined subset of non-small cell lung cancer. J Thorac Oncol 2009; 4(12): 1450–1454

    Article  PubMed  Google Scholar 

  122. Takeuchi K, Choi YL, Togashi Y, Soda M, Hatano S, Inamura K, Takada S, Ueno T, Yamashita Y, Satoh Y, Okumura S, Nakagawa K, Ishikawa Y, Mano H. KIF5B-ALK, a novel fusion oncokinase identified by an immunohistochemistry-based diagnostic system for ALK-positive lung cancer. Clin Cancer Res 2009; 15(9): 3143–3149

    Article  PubMed  CAS  Google Scholar 

  123. Rabkin CS, Janz S. Mechanisms and consequences of chromosomal translocation. Cancer Epidemiol Biomarkers Prev 2008; 17(8): 1849–1851

    Article  PubMed  CAS  Google Scholar 

  124. Wiemels J. Chromosomal translocations in childhood leukemia: natural history, mechanisms, and epidemiology. J Natl Cancer Inst Monogr 2008; 39: 87–90

    Article  PubMed  CAS  Google Scholar 

  125. Magrath I. Epidemiology: clues to the pathogenesis of Burkitt lymphoma. Br J Haematol 2012; 156(6): 744–756

    Article  PubMed  CAS  Google Scholar 

  126. Greaves MF, Wiemels J. Origins of chromosome translocations in childhood leukaemia. Nat Rev Cancer 2003; 3(9): 639–649

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Integrated Department of Immunology, University of Colorado School of Medicine and National Jewish Health, Denver, CO, 80206, USA

    Jing H. Wang

Authors
  1. Jing H. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jing H. Wang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, J.H. Mechanisms and impacts of chromosomal translocations in cancers. Front. Med. 6, 263–274 (2012). https://doi.org/10.1007/s11684-012-0215-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11684-012-0215-5

Keywords

Search

Navigation