Abstract
Reciprocal chromosomal translocations involving the immunoglobulin (Ig) loci are a hallmark of most mature B cell lymphomas and usually result in dysregulated expression of oncogenes brought under the control of the Ig enhancers. Although the precise mechanisms involved in the development of these translocations remains essentially unknown, a clear relationship has been established with the mechanisms that lead to Ig gene remodeling, including V(D)J recombination, isotype switching and somatic hypermutation. The common denominator of these three processes in the formation of Ig-associated translocations is probably represented by the fact that each of these processes intrinsically generates double-strand DNA breaks. Since isotype switching and somatic hypermutation occur in germinal center (GC) B cells, the origin of a large number of B cell lymphomas from GC B cells is likely closely related to aberrant hypermutation and isotype switching activity in these B cells.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Adachi M, Tsujimoto Y . 1989 Oncogene 4: 1073–1075
Adams JM, Harris AW, Pinkert CA, Corcoran LM, Alexander WS, Cory S, Palmiter RD, Brinster RL . 1985 Nature 318: 533–538
Agrawal A, Eastman QM, Schatz DG . 1998 Nature 394: 744–751
Akasaka H, Akasaka T, Kurata M, Ueda C, Shimizu A, Uchiyama T, Ohno H . 2000 Cancer Res. 60: 2335–2341
Aplan PD, Lombardi DP, Ginsberg AM, Cossman J, Bertness VL, Kirsch IR . 1990 Science 250: 1426–1429
Bakhshi A, Wright JJ, Graninger W, Seto M, Owens J, Cossman J, Jensen JP, Goldman P, Korsmeyer SJ . 1987 Proc. Natl. Acad. Sci. USA 84: 2396–2400
Baron BW, Nucifora G, McCabe N, Espinosa R, Le Beau MM, McKeithan TW . 1993 Proc. Natl. Acad. Sci. USA 90: 5262–5266
Berek C, Berger A, Apel M . 1991 Cell. 67: 1121–1129
Betz AG, Milstein C, Gonzalez-Fernandez A, Pannell R, Larson T, Neuberger MS . 1994 Cell. 77: 239–248
Bross L, Fukita Y, McBlane F, Demolliere C, Rajewsky K, Jacobs H . 2000 Immunity 13: 589–597
Brown L, Cheng JT, Chen Q, Siciliano MJ, Crist W, Buchanan G, Baer R . 1990 EMBO J. 9: 3343–3351
Callanan MB, Le Baccon P, Mossuz P, Duley S, Bastard C, Hamoudi R, Dyer MJ, Klobeck G, Rimokh R, Sotto JJ, Leroux D . 2000 Proc. Natl. Acad. Sci. USA 97: 309–314
Cario G, Stadt UZ, Reiter A, Welte K, Sykora KW . 2000 Br. J. Haematol. 110: 537–546
Cayuela JM, Gardie B, Sigaux F . 1997 Blood 90: 3720–3726
Chaganti SR, Rao PH, Chen W, Dyomin V, Jhanwar SC, Parsa NZ, Dalla-Favera R, Chaganti RS . 1998 Genes Chrom. Cancer 23: 328–336
Chesi M, Bergsagel PL, Shonukan OO, Martelli ML, Brents LA, Chen T, Schrock E, Ried T, Kuehl WM . 1998a Blood 91: 4457–4463
Chesi M, Nardini E, Brents LA, Schrock E, Ried T, Kuehl WM, Bergsagel PL . 1997 Nat. Genet. 16: 260–264
Chesi M, Nardini E, Lim RS, Smith KD, Kuehl WM, Bergsagel PL . 1998b Blood 92: 3025–3034
Chirmule N, Tazelaar J, Wilson JM . 2000 J. Immunol. 164: 248–255
Cotter F, Price C, Zucca E, Young BD . 1990 Blood 76: 131–135
Dalla-Favera R, Gaidano G . 2001 Cancer DeVita VT, Hellman S and Rosenberg SA. (eds). Lippincott Williams and Wilkins: Philadelphia, USA pp. 2215–2235
Dalla-Favera R, Martinotti S, Gallo RC, Erikson J, Croce CM . 1983 Science 219: 963–967
de Jong D, Voetdijk BM, Van Ommen GJ, Kluin-Nelemans JC, Beverstock GC, Kluin PM . 1989 J. Exp. Med. 169: 613–624
Denny CT, Hollis GF, Magrath IT, Kirsch IR . 1985 Mol. Cell. Biol. 5: 3199–3207
Fugmann SD, Lee AI, Shockett PE, Villey IJ, Schatz DG . 2000 Ann. Rev. Immunol. 18: 495–527
Fukita Y, Jacobs H, Rajewsky K . 1998 Immunity 9: 105–114
Fuscoe JC, Zimmerman LJ, Lippert MJ, Nicklas JA, O'Neill JP, Albertini RJ . 1991 Cancer Res. 51: 6001–6005
Fyfe G, Cebra-Thomas JA, Mustain E, Davie JM, Alley CD, Nahm MH . 1987 J. Immunol. 139: 2187–2194
Gabrea A, Bergsagel PL, Chesi M, Shou Y, Kuehl WM . 1999 Mol. Cell. 3: 119–123
Garcia de Vinuesa C, O'Leary P, Sze DM, Toellner KM, MacLennan IC . 1999 Eur. J. Immunol. 29: 1314–1323
Gardby E, Lycke NY . 2000 Eur. J. Immunol. 30: 1861–1871
Gartner F, Alt FW, Monroe RJ, Seidl KJ . 2000 J. Exp. Med. 192: 1745–1754
Gelmann EP, Psallidopoulos MC, Papas TS, Dalla-Favera R . 1983 Nature 306: 799–803
Gilles F, Goy A, Remache Y, Shue P, Zelenetz AD . 2000 Blood 95: 2930–2936
Girschick HJ, Grammer AC, Nanki T, Mayo M, Lipsky PE . 2001 J. Immunol. 166: 377–386
Goossens T, Klein U, Küppers R . 1998 Proc. Natl. Acad. Sci. USA 95: 2463–2468
Goyenechea B, Milstein C . 1996 Proc. Natl. Acad. Sci. USA 93: 13979–13984
Gronbaek K, Straten PT, Ralfkiaer E, Ahrenkiel V, Andersen MK, Hansen NE, Zeuthen J, Hou-Jensen K, Guldberg P . 1998 Blood 92: 3018–3024
Haluska FG, Finver S, Tsujimoto Y, Croce CM . 1986 Nature 324: 158–161
Han S, Dillon SR, Zheng B, Shimoda M, Schlissel MS, Kelsoe G . 1997 Science 278: 301–305
Harrison CJ . 2000 Baillieres Best Pract. Res. Clin. Haematol. 13: 427–439
Hartl P, Lipp M . 1987 Mol. Cell. Biol. 7: 2037–2045
Hatzivassiliou G, Miller I, Takizawa J, Palanisamy N, Pulivarthi R, Iida S, Tagawa S, Russo J, Neri A, Cattoretti G, Clynes R, Mendelsohn C, Chaganti RSK, Dalla-Favera R . 2001 Immunity 14: 277–289
Henglein B, Synovzik H, Groitl P, Bornkamm GW, Hartl P, Lipp M . 1989 Mol. Cell. Biol. 9: 2105–2113
Hiom K, Melek M, Gellert M . 1998 Cell 94: 463–470
Hollis GF, Mitchell KF, Battey J, Potter H, Taub R, Lenoir GM, Leder P . 1984 Nature 307: 752–755
Iida S, Rao PH, Butler M, Corradini P, Boccadoro M, Klein B, Chaganti RS, Dalla-Favera R . 1997 Nat. Genet. 17: 226–230
Iida S, Rao PH, Nallasivam P, Hibshoosh H, Butler M, Louie DC, Dyomin V, Ohno H, Chaganti RS, Dalla-Favera R . 1996 Blood 88: 4110–4117
Irsch J, Irlenbusch S, Radl J, Burrows PD, Cooper MD, Radbruch AH . 1994 Proc. Natl. Acad. Sci. USA 91: 1323–1327
Isaacson PG . 1996 Histopathology 28: 487–495
Jacob J, Kelsoe G, Rajewsky K, Weiss U . 1991 Nature 354: 389–392
Jaeger U, Karth GD, Knapp S, Friedl J, Laczika K, Kusec R . 1994 Leuk. Lymphoma 14: 197–202
Jaeger U, Purtscher B, Karth GD, Knapp S, Mannhalter C, Lechner K . 1993 Blood 81: 1833–1840
Jäger U, Bocskor S, Le T, Mitterbauer G, Bolz I, Chott A, Kneba M, Mannhalter C, Nadel B . 2000 Blood 95: 3520–3529
Janssen JW, Vaandrager JW, Heuser T, Jauch A, Kluin PM, Geelen E, Bergsagel PL, Kuehl WM, Drexler HG, Otsuki T, Bartram CR, Schuuring E . 2000 Blood 95: 2691–2698
Kanzler H, Küppers R, Hansmann ML, Rajewsky K . 1996 J. Exp. Med. 184: 1495–1505
Kato S, Tachibana K, Takayama N, Kataoka H, Yoshida MC, Takano T . 1991 Gene 97: 239–244
Kinzler KW, Vogelstein B . 1996 Cell 87: 159–170
Kirsch IR, Lista F . 1997 Semin. Immunol. 9: 207–215
Klein U, Goossens T, Fischer M, Kanzler H, Braeuninger A, Rajewsky K, Küppers R . 1998a Immunol. Rev. 162: 261–280
Klein U, Rajewsky K, Küppers R . 1998b J. Exp. Med. 188: 1679–1689
Klobeck HG, Combriato G, Zachau HG . 1987 Nucleic Acids Res. 15: 4877–4888
Komatsu H, Iida S, Yamamoto K, Mikuni C, Nitta M, Takahashi T, Ueda R, Seto M . 1994 Blood 84: 1226–1231
Küppers R, Goossens T, Klein U . 1999a Curr. Top. Microbiol. Immunol. 246: 193–198
Küppers R, Klein U, Hansmann ML, Rajewsky K . 1999b N. Engl. J. Med. 341: 1520–1529
Küppers R, Rajewsky K . 1998 Ann. Rev. Immunol. 16: 471–493
Küppers R, Zhao M, Hansmann ML, Rajewsky K . 1993 EMBO J. 12: 4955–4967
Lam KP, Kühn R, Rajewsky K . 1997 Cell 90: 1073–1083
Landowski TH, Qu N, Buyuksal I, Painter JS, Dalton WS . 1997 Blood 90: 4266–4270
Li YS, Hayakawa K, Hardy RR . 1993 J. Exp. Med. 178: 951–960
Limpens J, de Jong D, van Krieken JH, Price CG, Young BD, van Ommen GJ, Kluin PM . 1991 Oncogene 6: 2271–2276
Liu YJ, Malisan F, de Bouteiller O, Guret C, Lebecque S, Banchereau J, Mills FC, Max EE, Martinez-Valdez H . 1996 Immunity 4: 241–250
MacLennan IC . 1994 Ann. Rev. Immunol. 12: 117–139
Maizels N . 1999 Am. J. Hum. Genet. 64: 1270–1275
Maizels N, Bothwell A . 1985 Cell 43: 715–720
Matsumoto M, Mariathasan S, Nahm MH, Baranyay F, Peschon JJ, Chaplin DD . 1996 Science 271: 1289–1291
McDonnell TJ, Korsmeyer SJ . 1991 Nature 349: 254–256
McKeithan TW, Takimoto GS, Ohno H, Bjorling VS, Morgan R, Hecht BK, Dube I, Sandberg AA, Rowley JD . 1997 Genes Chrom. Cancer 20: 64–72
Meffre E, Davis E, Schiff C, Cunningham-Rundles C, Ivashkiv LB, Staudt LM, Young JW, Nussenzweig MC . 2000 Nature Immunol. 1: 207–213
Meffre E, Papavasiliou F, Cohen P, de Bouteiller O, Bell D, Karasuyama H, Schiff C, Banchereau J, Liu YJ, Nussenzweig MC . 1998 J. Exp. Med. 188: 765–772
Meijerink JP, Raemaekers JM, Mensink EJ . 1995 Br. J. Haematol. 91: 630–639
Migliazza A, Martinotti S, Chen W, Fusco C, Ye BH, Knowles DM, Offit K, Chaganti RS, Dalla-Favera R . 1995 Proc. Natl. Acad. Sci. USA 92: 12520–12524
Muller JR, Janz S, Goedert JJ, Potter M, Rabkin CS . 1995 Proc. Natl. Acad. Sci. USA 92: 6577–6581
Müschen M, Re D, Bräuninger A, Wolf J, Hansmann ML, Diehl V, Küppers R, Rajewsky K . 2000a Cancer Res. 60: 5640–5643
Müschen M, Re D, Jungnickel B, Diehl V, Rajewsky K, Küppers R . 2000b J. Exp. Med. 192: 1833–1840
Neri A, Barriga F, Knowles DM, Magrath IT, Dalla-Favera R . 1988 Proc. Natl. Acad. Sci. USA 85: 2748–2752
Neri A, Chang CC, Lombardi L, Salina M, Corradini P, Maiolo AT, Chaganti RS, Dalla-Favera R . 1991 Cell 67: 1075–1087
Neuberger MS, Milstein C . 1995 Curr. Opin. Immunol. 7: 248–254
Ohno H, Doi S, Yabumoto K, Fukuhara S, McKeithan TW . 1993 Leukemia 7: 2057–2063
Papavasiliou F, Casellas R, Suh H, Qin XF, Besmer E, Pelanda R, Nemazee D, Rajewsky K, Nussenzweig MC . 1997 Science 278: 298–301
Papavasiliou FN, Schatz DG . 2000 Nature 408: 216–221
Pasqualucci L, Migliazza A, Fracchiolla N, William C, Neri A, Baldini L, Chaganti RSK, Klein U, Küppers R, Rajewsky K, Dalla-Favera R . 1998 Proc. Natl. Acad. Sci. USA 95: 11816–11821
Pasqualucci L, Neumeister P, Gossers T, Nanjangud G, Chaganti RSK, Küppers R, Dalla-Favera R . 2001 Nature in press
Peng HZ, Du MQ, Koulis A, Aiello A, Dogan A, Pan LX, Isaacson PG . 1999 Blood 93: 2167–2172
Peters A, Storb U . 1996 Immunity 4: 57–65
Rajewsky K . 1996 Nature 381: 751–758
Roschke V, Kopantzev E, Dertzbaugh M, Rudikoff S . 1997 Oncogene 14: 3011–3016
Roth DB, Craig NL . 1998 Cell 94: 411–414
Rowley JD . 1999 Semin. Hematol. 36: 59–72
Shen HM, Peters A, Baron B, Zhu X, Storb U . 1998 Science 280: 1750–1752
Shou Y, Martelli ML, Gabrea A, Qi Y, Brents LA, Roschke A, Dewald G, Kirsch IR, Bergsagel PL, Kuehl WM . 2000 Proc. Natl. Acad. Sci. USA 97: 228–233
Showe LC, Ballantine M, Nishikura K, Erikson J, Kaji H, Croce CM . 1985 Mol. Cell. Biol. 5: 501–509
Siminovitch KA, Bakhshi A, Goldman P, Korsmeyer SJ . 1985 Nature 316: 260–262
Summers KE, Goff LK, Wilson AG, Gupta RK, Lister TA, Fitzgibbon J . 2001 J. Clin. Oncol. 19: 420–424
Takakuwa T, Dong Z, Takayama H, Matsuzuka F, Nagata S, Aozasa K . 2001 Cancer Res. 61: 1382–1385
Taub R, Kirsch I, Morton C, Lenoir G, Swan D, Tronick S, Aaronson S, Leder P . 1982 Proc. Natl. Acad. Sci. USA 79: 7837–7841
Tonegawa S . 1983 Nature 302: 575–581
Tsujimoto Y, Gorham J, Cossman J, Jaffe E, Croce CM . 1985 Science 229: 1390–1393
Tsujimoto Y, Louie E, Bashir MM, Croce CM . 1988 Oncogene 2: 347–351
Tycko B, Palmer JD, Sklar J . 1989 Science 245: 1242–1246
Tycko B, Sklar J . 1990 Cancer Cells 2: 1–8
Vaandrager JW, Schuuring E, Kluin-Nelemans HC, Dyer MJS, Raap AK, Kluin PM . 1998 Blood 92: 2871–2878
Vaandrager JW, Schuuring E, Philippo K, Kluin PM . 2000 Blood 96: 1947–1952
Weller S, Faili A, Garcia C, Braun MC, Le Deist FF, de Saint Basile GG, Hermine O, Fischer A, Reynaud CA, Weill JC . 2001 Proc. Natl. Acad. Sci. USA 98: 1166–1170
Welzel N, Le T, Marculescu R, Mitterbauer G, Chott A, Pott C, Kneba M, Du M-Q, Kusec R, Drach J, Raderer M, Mannhalter C, Lechner K, Nadel B, Jaeger U . 2001 Cancer Res. 61: 1629–1636
Willis TG, Dyer MJ . 2000 Blood 96: 808–822
Willis TG, Jadayel DM, Du MQ, Peng H, Perry AR, Abdul-Rauf M, Price H, Karran L, Majekodunmi O, Crook T, Hamoudi R, Isaacson PG, Dyer MJS . 1999 Cell 96: 35–45
Willis TG, Zalcberg IR, Coignet LJ, Wlodarska I, Stul M, Jadayel DM, Bastard C, Treleaven JG, Catovsky D, Silva ML, Dyer MJ . 1998 Blood 91: 1873–1881
Wyatt RT, Rudders RA, Zelenetz A, Delellis RA, Krontiris TG . 1992 J. Exp. Med. 175: 1575–1588
Ye BH, Rao PH, Chaganti RS, Dalla-Favera R . 1993 Cancer Res. 53: 2732–2735
Yoshida S, Kaneita Y, Aoki Y, Seto M, Mori S, Moriyama M . 1999 Oncogene 18: 7994–7999
Yu W, Nagaoka H, Jankovic M, Misulovin Z, Suh H, Rolink A, Melchers F, Meffre E, Nussenzweig MC . 1999 Nature 400: 682–687
Zhang K, Cheah HK, Saxon A . 1995 J. Immunol. 154: 2237–2247
Zhang Q, Siebert R, Yan M, Hinzmann B, Cui X, Xue L, Rakestraw KM, Naeve CW, Beckmann G, Weisenburger DD, Sanger WG, Nowotny H, Vesely M, Callet-Bauchu E, Salles G, Dixit VM, Rosenthal A, Schlegelberger B, Morris SW . 1999 Nat. Genet. 22: 63–68
Acknowledgements
R Küppers is supported by the Deutsche Forschungsgemeinschaft through SFB502 and the Heisenberg programme. We thank Richard Baer for critically reading the manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Küppers, R., Dalla-Favera, R. Mechanisms of chromosomal translocations in B cell lymphomas. Oncogene 20, 5580–5594 (2001). https://doi.org/10.1038/sj.onc.1204640
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1204640
Keywords
This article is cited by
-
Emerging entities: high-grade/large B-cell lymphoma with 11q aberration, large B-cell lymphoma with IRF4 rearrangement, and new molecular subgroups in large B-cell lymphomas. A report of the 2022 EA4HP/SH lymphoma workshop
Virchows Archiv (2023)
-
Burkitt lymphoma
Nature Reviews Disease Primers (2022)
-
Biological and clinical significance of epigenetic alterations in B-cell lymphomas
International Journal of Hematology (2022)
-
Molecular Subgroups of Diffuse Large B Cell Lymphoma: Biology and Implications for Clinical Practice
Current Oncology Reports (2022)
-
An international working group consensus report for the prioritization of molecular biomarkers for Ewing sarcoma
npj Precision Oncology (2022)