Neoplasias Involving Translocation of Antigen Receptor Genes


Cytogenetic analysis of neoplastic lymphoid tissues isolated from humans typically reveals chromosomal abnormalities. Although direct causal relationships between specific genetic anomalies and tumorigenesis are complex, these relationships are probably better defined for hematological diseases than for solid tumors. Observations on large numbers of hematological tumors have resulted in the description of numerous nonrandom genetic lesions that are associated with specific and well-defined tumors.


Transgenic Mouse Acute Lymphoblastic Leukemia Chronic Lymphocytic Leukemia Chromosomal Translocation BCL6 Gene 
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  1. 1.
    Griesser, H., Tkachuk, D., Reis, M. D., and Mak, T. W. 1989. Gene rearrangements and translocations in lymphoproliferative diseases. Blood 73:1402–1415.PubMedGoogle Scholar
  2. 2.
    Tycko, B., and Sklar, J. 1990. Chromosomal translocations in lymphoid neoplasia: A reappraisal of the recombinase model. Cancer Cells 2:1–8.PubMedGoogle Scholar
  3. 3.
    Lichty, B. D., Ackland Snow, J., Noble, L., Kamel Reid, S., and Dube, I. D. 1995. Dysregulation of HOX11 by chromosome translocations in T-cell acute lymphoblastic leukemia: A paradigm for homeobox gene involvement in human cancer. Leuk. Lymphoma 16:209–215.PubMedGoogle Scholar
  4. 4.
    Dube, I. D., Raimondi, S. C, Pi, D., and Kalousek, D. K. 1986. A new translation, t(10;14)(q24;q11), in T cell neoplasia. Blood 67:1181–1184.PubMedGoogle Scholar
  5. 5.
    Raimondi, S. C. 1993. Current status of cytogenetic research in childhood acute lymphoblastic leukemia. Blood 81:2237–2251.PubMedGoogle Scholar
  6. 6.
    Hatano, M., Roberts, C. W., Minden, M., Crist, W. M., and Korsmeyer, S. J. 1991. Deregulation of a homeobox gene, HOX11, by the t(10;l4) in T cell leukemia. Science 253:79–82.PubMedCrossRefGoogle Scholar
  7. 7.
    Kennedy, M. A., Gonzalez Sarmiento, R., Kees, U. R., Lampert, F., Dear, N., Boehm, T., and Rabbitts, T. H. 1991. HOX11, a homeobox-containing T-cell oncogene on human chromosome 10q24. Proc. Natl. Acad. Sci. USA 88:8900–8904.PubMedCrossRefGoogle Scholar
  8. 8.
    Roberts, C. W., Shutter, J. R., and Korsmeyer, S. J. 1994. Hox11 controls the genesis of the spleen. Nature 368:747–749.PubMedCrossRefGoogle Scholar
  9. 9.
    Dube, I. D., Kamel Reid, S., Yuan, C. C., Lu, M., Wu, X., Corpus, G., Raimondi, S. C., Crist, W. M., Carroll, A. J., Minowada, J., and Baker, J. B. 1991. A novel human homeobox gene lies at the chromosome 10 breakpoint in lymphoid neoplasias with chromosomal translocation t(10; 14). Blood 78:2996–3003.PubMedGoogle Scholar
  10. 10.
    Lu, M., Zhang, N., and Ho, A. D. 1992. Genomic organization of the putative human homeobox protooncogene HOX-11 (TCL-3) and its endogenous expression in T cells. Oncogene 7:1325–1330.PubMedGoogle Scholar
  11. 11.
    Hatano, M., Roberts, C. W. M., Kawabe, T., Shutter, J., and Korsmeyer, S. J. 1995. Cell cycle progression, cell death and T-cell lymphoma in HOX11 transgenic mice. Blood 80(Suppl.):355a.Google Scholar
  12. 12.
    Hawley, R. G., Fong, A. Z., Lu, M., and Hawley, T. S. 1994. The HOX11 homeobox-containing gene of human leukemia immortalizes murine hematopoietic precursors. Oncogene 9:1–12.PubMedGoogle Scholar
  13. 13.
    Duro, D., Bernard, O., Della Valle, V., Leblanc, T., Berger, R., and Larsen, C. J. 1996. Inactivation of the P16INK4/MTS1 gene by a chromosome translocation t(9; 14)(p21–22;q11) in an acute lymphoblastic leukemia of B-cell type. Cancer Res. 56:848–854.PubMedGoogle Scholar
  14. 14.
    Iolascon, A., Faienza, M. F., Coppola, B., della Ragione, F., Schettini, F., and Biondi, A. 1996. Homozygous deletions of cyclin-dependent kinase inhibitor genes, p16(INK4A) and p18, in childhood T cell lineage acute lymphoblastic leukemias. Leukemia 10:255–260.PubMedGoogle Scholar
  15. 15.
    Saxena, A., Robertson, J. T., and Ali, I. U. 1996. Abnormalities of p16, p15 and CDK4 genes in recurrent malignant astrocytomas. Oncogene 13:661–664.PubMedGoogle Scholar
  16. 16.
    FitzGerald, M. G., Harkin, D. P., Silva Arrieta, S., MacDonald, D. J., Lucchina, L. C., Unsal, H., O’Neill, E., Koh, J., Finkelstein, D. M., Isselbacher, K. J., Sober, A. J., and Haber, D. A. 1996. Prevalence of germ-line mutations in p16, p19ARF, and CDK4 in familial melanoma: Analysis of a clinic-based population. Proc. Natl. Acad. Sci. USA 93:8541–8545.PubMedCrossRefGoogle Scholar
  17. 17.
    Reed, A. L., Califano, J., Cairns, P., Westra, W. H., Jones, R. M., Koch, W., Ahrendt, S., Eby, Y., Sewell, D., Nawroz, H., Bartek, J., and Sidransky, D. 1996. High frequency of p16 (CDKN2/MTS1/INK4A) inactivation in head and neck squamous cell carcinoma. Cancer Res. 56:3630–3633.PubMedGoogle Scholar
  18. 18.
    Kees, U. R., Ranford, P. R., and Hatzis, M. 1996. Deletions of the p16 gene in pediatric leukemia and corresponding cell lines. Oncogene 12:2235–2239.PubMedGoogle Scholar
  19. 19.
    Lo, K. W., Cheung, S. T., Leung, S. F., van Hasselt, A., Tsang, Y. S., Mak, K. F., Chung, Y. F., Woo, J. K., Lee, J. C., and Huang, D. P. 1996. Hypermethylation of the p16 gene in nasopharyngeal carcinoma. Cancer Res. 56:2721–2725.PubMedGoogle Scholar
  20. 20.
    Borg, A., Johannsson, U., Johannsson, O., Haekansson, S., Westerdahl, J., Maesbaeck, A., Olsson, H., and Ingvar, C. 1996. Novel germline p16 mutation in familial malignant melanoma in southern Sweden. Cancer Res. 56:2497–2500.PubMedGoogle Scholar
  21. 21.
    Geradts, J., and Wilson, P. A. 1996. High frequency of aberrant p16(lNK4A) expression in human breast cancer. Am. J. Pathol. 149:15–20.PubMedGoogle Scholar
  22. 22.
    Tycko, B., Smith, S. D., and Sklar, J. 1991. Chromosomal translocations joining LCK and TCRB loci in human T cell leukemia. J. Exp. Med. 174:867–873.PubMedCrossRefGoogle Scholar
  23. 23.
    Molina, T. J., Bachmann, M. F., Kundig, T. M., Zinkernagel, R. M., and Mak, T. W. 1993. Peripheral T cells in mice lacking p56Ick do not express significant antiviral effector functions. J. Immunol. 151:699–706.PubMedGoogle Scholar
  24. 24.
    Penninger, J., Kishihara, K., Molina, T., Wallace, V. A., Timms, E., Hedrick, S. M., and Mak, T. W. 1993. Requirement for tyrosine kinase p56Ick for thymic development of transgenic gamma delta T cells. Science 260:358–361.PubMedCrossRefGoogle Scholar
  25. 25.
    Fischer, S., Marie Cardine, A., Ramos Morales, F., Bougeret, C., Soula, M., Maridonneau Parini, I., and Benarous, R. 1994. P56Ick A lymphocyte specific protein tyrosine kinase: Activation, regulation and signal transduction. Cell. Mol Biol. 40:605–609.PubMedGoogle Scholar
  26. 26.
    Perlmutter, R. M. 1995. Control of T cell development by non-receptor protein tyrosine kinases. Cancer Sun: 22:85–95.Google Scholar
  27. 27.
    Penninger, J. M., Wallace, V. A., Kishihara, K., and Mak, T. W. 1993. The role of p56Ick and p59fyn tyrosine kinases and CD45 protein tyrosine phosphatase in T-cell development and clonal selection. Immunol. Rev. 135:183–214.PubMedCrossRefGoogle Scholar
  28. 28.
    Molina, T. J., Kishihara, K., Siderovski, D. P., van Ewijk, W., Narendran, A., Timms, E., Wakeham, A., Paige, C. J., Hartmann, K. U., Veillette, A., Davidson, D., and Mak, T. W. 1992. Profound block in thymocyte development in mice lacking p56Ick. Nature 357:161–164.PubMedCrossRefGoogle Scholar
  29. 29.
    Wright, D. D., Sefton, B. M., and Kamps, M. P. 1994. Oncogenic activation of the Lck protein accompanies translocation of the LCK gene in the human HSB2 T-cell leukemia. Mol. Cell. Biol. 14:2429–2437.PubMedGoogle Scholar
  30. 30.
    Burnett, R. C., Thirman, M. J., Rowley, J. D., and Diaz, M. O. 1994. Molecular analysis of the T-cell acute lymphoblastic leukemia-associated t(1;7)(p34;q34) that fuses LCK and TCRB. Blood 84:1232–1236.PubMedGoogle Scholar
  31. 31.
    Shima, E. A., Le Beau, M. M., McKeithan, T. W., Minowada, J., Showe, L. C, Mak, T. W., Minden, M. D., Rowley, J. D., and Diaz, M. O. 1986. Gene encoding the alpha chain of the T-cell receptor is moved immediately downstream of c-myc in a chromosomal 8; 14 translocation in a cell line from a human T-cell leukemia. Proc. Natl. Acad. Sci. USA 83:3439–3443.PubMedCrossRefGoogle Scholar
  32. 32.
    Rabbitts, T. H., and Boehm, T. 1991. Structural and functional chimerism results from chromosomal translocation in lymphoid tumors. Adv. Immunol. 50:119–146.PubMedCrossRefGoogle Scholar
  33. 33.
    Morgenbesser, S. D., and DePinho, R. A. 1994. Use of transgenic mice to study myc family gene function in normal mammalian development and in cancer. Semin. Cancer Biol. 5:21–36.PubMedGoogle Scholar
  34. 34.
    Packham, G., and Cleveland, J. L. 1995. c-Myc and apoptosis. Biochim. Biophys. Acta 1242:11–28.PubMedGoogle Scholar
  35. 35.
    Blackwood, E. M., and Eisenman, R. N. 1991. Max: A helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc. Science 251:1211–1217.PubMedCrossRefGoogle Scholar
  36. 36.
    Prendergast, G. C., Lawe, D., and Ziff, E. B. 1991. Association of Myn, the murine homolog of max, with c-Myc stimulates methylation-sensitive DNA binding and ras cotransformation. Cell 65:395–407.PubMedCrossRefGoogle Scholar
  37. 37.
    Ayer, D. E., Kretzner, L., and Eisenman, R. N. 1993. Mad: A heterodimeric partner for Max that antagonizes Myc transcriptional activity. Cell 72:211–222.PubMedCrossRefGoogle Scholar
  38. 38.
    Zervos, A. S., Gyuris, J., and Brent, R. 1993. Mxil, a protein that specifically interacts with Max to bind Myc-Max recognition sites. Cell 72:223–232.PubMedCrossRefGoogle Scholar
  39. 39.
    Amati, B., Brooks, M. W., Levy, N., Littlewood, T. D., Evan, G. I., and Land, H. 1993. Oncogenic activity of the c-Myc protein requires dimerization with Max. Cell 72:233–245.PubMedCrossRefGoogle Scholar
  40. 40.
    Shrivastava, A., and Calame, K. 1995. Association with c-Myc: An alternated mechanism for c-Myc function. Curr. Top. Microbiol. Immunol. 194:273–282.PubMedGoogle Scholar
  41. 41.
    Fisch, P., Forster, A., Sherrington, P. D., Dyer, M. J., and Rabbitts, T. H. 1993. The chromosomal translocation t(X;14)(q28;q11) in T-cell pro-lymphocytic leukaemia breaks within one gene and activates another. Oncogene 8:3271–3276.PubMedGoogle Scholar
  42. 42.
    Stern, M. H., Soulier, J., Rosenzwajg, M., Nakahara, K., Canki Klain, N., Aurias, A., Sigaux, F., and Kirsch, I. R. 1993. MTCP-1: A novel gene on the human chromosome Xq28 translocated to the T cell receptor alpha/delta locus in mature T cell proliferations. Oncogene 8:2475–2483.PubMedGoogle Scholar
  43. 43.
    Soulier, J., Madani, A., Cacheux, V., Rosenzwajg, M., Sigaux, F., and Stern, M. H. 1994. The MTCP-1/c6.IB gene encodes for a cytoplasmic 8 kD protein overexpressed in T cell leukemia bearing a t(X;14) translocation. Oncogene 9:3565–3570.PubMedGoogle Scholar
  44. 44.
    Taylor, A. M., Lowe, P. A., Stacey, M., Thick, J., Campbell, L., Beatty, D., Biggs, P., and Formstone, C. J. 1992. Development of T-cell leukaemia in an ataxia telangiectasia patient following clonal selection in t(X;14)-containing lymphocytes. Leukemia 6:961–966.PubMedGoogle Scholar
  45. 45.
    Madani, A., Soulier, J., Schmid, M., Plichtova, R., Lerme, F., Gateauroesch, O., Garnier, J. P., Pla, M., Sigaux, F., and Stern, M. H. 1995. The 8-KD product of the putative oncogene MTCP-1 is a mitochondrial protein. Oncogene 10:2259–2262.PubMedGoogle Scholar
  46. 46.
    Fu, T. B., Virgilio, L., Narducci, M. G., Facchiano, A., Russo, G., and Croce, C. M. 1994. Characterization and localization of the TCL-1 oncogene product. Cancer Res. 54:6297–6301.PubMedGoogle Scholar
  47. 47.
    Baer, R. 1993. TAL1, TAL2 and LYL1: A family of basic helix-loop-helix proteins implicated in T cell acute leukaemia. Semin. Cancer Biol. 4:341–347.PubMedGoogle Scholar
  48. 48.
    Bash, R. O., Hall, S., Timmons, C. F., Crist, W. M., Amylon, M., Smith, R. G., and Baer, R. 1995. Does activation of the TAL1 gene occur in a majority of patients with T-cell acute lymphoblaslic leukemia? A Pediatric Oncology Group study. Blood 86:666–676.PubMedGoogle Scholar
  49. 49.
    Brown, L., Cheng, J. T., Chen, Q., Siciliano, M. J., Crist, W., Buchanan, G., and Baer, R. Site-specific recombination of the tal-1 gene is a common occurrence in human T cell leukemia. EMBO J. 9:3343–3351.Google Scholar
  50. 50.
    Carroll, A. J., Crist, W. M., Link, M. P., Amylon, M. D., Pullen, D. J., Ragab, A. H., Buchanan, G. R., Wimmer, R. S., and Vietti, T. J. 1990. The t(1;14)(p34;q11) is nonrandom and restricted to T-cell acute lymphoblastic leukemia: A Pediatric Oncology Group study. Blood 76:1220–1224.PubMedGoogle Scholar
  51. 51.
    Shivdasani, R. A., Mayer, E. L., and Orkin, S. H. 1995. Absence of blood formation in mice lacking the T-cell leukaemia oncoprotein Tal-1/SCL. Nature 373:432–434.PubMedCrossRefGoogle Scholar
  52. 52.
    Virgilio, L., Narducci, M. G., Isobe, M., Billips, L. G., Cooper, M. D., Croce, C. M., and Russo, G. 1994. Identification of the TCL1 gene involved in T-cell malignancies. Proc. Natl. Acad. Sci. USA 91:12530–12534.PubMedCrossRefGoogle Scholar
  53. 53.
    Mengle Gaw, L., Willard, H. F., Smith, C. I., Hammarstroem, L., Fischer, P., Sherrington, P., Lucas, G., Thompson, P. W., Baer, R., and Rabbitts, T. H. 1987. Human T-cell tumours containing chromosome 14 inversion or translocation with breakpoints proximal to immunoglobulin joining regions at 14q32. EMBO J. 6:2273–2280.PubMedGoogle Scholar
  54. 54.
    Matutes, E., Brito Babapulle, V., Swansbury, J., Ellis, J., Morilla, R., Dearden, C., Sempere, A., and Catovsky, D. 1991. Clinical and laboratory features of 78 cases of T-prolymphocytic leukemia. Blood 78:3269–3274.PubMedGoogle Scholar
  55. 55.
    Narducci, M. G., Virgilio, L., Isobe, M., Stoppacciaro, A., Elli, R., Fiorilli, M., Carbonari, M., Antonelli, A., Chessa, L., Croce, C. M., and Russo, G. 1995. TCL1 oncogene activation in preleukemic T-cells from a case of ataxis-telangiectasia. Blood 86:2358–2364.PubMedGoogle Scholar
  56. 56.
    Lindsell, C. E., Shawber, C. J., Boulter, J., and Weinmaster, G. 1995. Jagged: A mammalian ligand that activates Notch1. Cell 80:909–917.PubMedCrossRefGoogle Scholar
  57. 57.
    Ellisen, L. W., Bird, J., West, D. C., Soreng, A. L., Reynolds, T. C., Smith, S. D., and Sklar, J. 1991. TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell 66:649–661.PubMedCrossRefGoogle Scholar
  58. 58.
    Struhl, G., Fitzgerald, K., and Greenwald, I. 1993. Intrinsic activity of the Lin-12 and Notch intracellular domains in vivo. Cell 74:331–345.PubMedCrossRefGoogle Scholar
  59. 59.
    Chenn, A., and McConnell, S. K. 1995. Cleavage orientation and the asymmetric inheritance of notch 1 immunoreactivity in mammmalian neurogenesis. Cell 82:631–641.PubMedCrossRefGoogle Scholar
  60. 60.
    Nye, J. S., and Kopan, R. 1995. Developmental signaling—Vertebrate ligands for notch. Curr. Biol. 5:966–969.PubMedCrossRefGoogle Scholar
  61. 61.
    Fortini, M. E., and Artavanis Tsakonas, S. 1993. Notch: Neurogenesis is only part of the picture. Cell 75:1245–1247.PubMedCrossRefGoogle Scholar
  62. 62.
    Swiatek, P. J., Lindsell, C. E., del Amo, F. F., Weinmaster, G., and Gridley, T. 1994. Notch 1 is essential for postimplantation development in mice. Genes Dev. 8:707–719.PubMedCrossRefGoogle Scholar
  63. 63.
    Larsson, C., Lardelli, M., White, I., and Lendahl, U. 1994. The human NOTCH 1, 2, and 3 genes are located at chromosome positions 9q34. 1p13-p11, and 19p13.2-p13.1 in regions of neoplasia-associated translocation. Genomics 24:253–258.PubMedCrossRefGoogle Scholar
  64. 64.
    Sanchez Garcia, I., and Rabbitts, T. H. 1993. LIM domain proteins in leukaemia and development. Semin. Cancer Biol. 4:349–358.PubMedGoogle Scholar
  65. 65.
    Kaneko, Y., Frizzera, G., Shikano, T., Kobayashi, H., Maseki, N., and Sakurai, M. 1989. Chromosomal and immunophenotypic patterns in T cell acute lymphoblastic leukemia (T ALL) and lymphoblastic lymphoma (LBL). Leukemia 3:886–892.PubMedGoogle Scholar
  66. 66.
    Ribeiro, R. C., Raimondi, S. C., Behm, F. G., Cherrie, J., Crist, W. M., and Pui, C. H. 1991. Clinical and biologic features of childhood T-cell leukemia with the t(11;14). Blood 78:466–470.PubMedGoogle Scholar
  67. 67.
    Wadman, I., Li, J., Bash, R. O., Forster, A., Osada, H., Rabbitts, T. H., and Baer, R. 1994. Specific in vivo association between the bHLH and LIM proteins implicated in human T cell leukemia. EMBO J. 13:4831–4839.PubMedGoogle Scholar
  68. 68.
    McGuire, E. A., Rintoul, C. E., Sclar, G. M., and Korsmeyer, S. J. 1992. Thymic overexpression of Ttg-1 in transgenic mice results in T-cell acute lymphoblastic leukemia/lymphoma. Mol. Cell. Biol. 12:4186–4196.PubMedGoogle Scholar
  69. 69.
    Warren, A. J., Colledge, W. H., Carlton, M. B., Evans, M. J., Smith, A. J., and Rabbitts, T. H. 1994. The oncogenic cysteine-rich LIM domain protein rbtn2 is essential for erythroid development. Cell 78:45–57.PubMedCrossRefGoogle Scholar
  70. 70.
    Boehm, T., Spillantini, M. G., Sofroniew, M. V., Surani, M. A., and Rabbitts, T. H. 1991. Developmentally regulated and tissue specific expression of mRNAs encoding the two alternative forms of the LIM domain oncogene rhombotin: Evidence for thymus expression. Oncogene 6:695–703.PubMedGoogle Scholar
  71. 71.
    Greenberg, J. M., Boehm, T., Sofroniew, M. V., Keynes, R. J., Barton, S. C., Norris, M. L., Surani, M. A., Spillantini, M. G., and Rabbits, T. H. 1990. Segmental and developmental regulation of a presumptive T-cell oncogene in the central nervous system. Nature 344:158–160.PubMedCrossRefGoogle Scholar
  72. 72.
    Mcguire, E. A., Davis, A. R., and Korsmeyer, S. J. 1991. T-cell translocation gene 1 (Ttg-1) encodes a nuclear protein normally expressed in neural lineage cells. Blood 77:599–606.PubMedGoogle Scholar
  73. 73.
    Royer Pokora, B., Loos, U., and Ludwig, W. D. 1991. TTG-2, a new gene encoding a cysteine-rich protein with the LIM motif, is overexpressed in acute T-cell leukaemia with the t(11;14)(p13;q11). Oncogene 6:1887–1893.PubMedGoogle Scholar
  74. 74.
    Royer Pokora, B., Rogers, M., Zhu, T. H., Schneider, S., Loos, U., and Boelitz, U. 1995. The TTG-2/ RBTN2 T cell oncogene encodes two alternative transcripts from two promoters: The distal promoter is removed by most 11p13 translocations in acute T cell leukaemia (T-ALL). Oncogene 10:1353–1360.PubMedGoogle Scholar
  75. 75.
    Athan, F., Foitl, D. R., and Knowles, D. M. 1991. BCL-1 rearrangement. Frequency and clinical significance among B-cell chronic lymphocytic leukemias and non-Hodgkin’s lymphomas. Am. J. Pathol. 138:591–599.PubMedGoogle Scholar
  76. 76.
    Williams, M. E., Meeker, T. C., and Swerdlow, S. H. 1991. Rearrangement of the chromosome 11 bcl-1 locus in centrocytic lymphoma: Analysis with multiple breakpoint probes. Blood 78:493–498.PubMedGoogle Scholar
  77. 77.
    Raghoebier, S., van Krieken, J. H., Kluin Nelemans, J. C., Gillis, A., van Ommen, G. J., Ginsberg, A. M., Raffeld, M., and Kluin, P. M. 1991. Oncogene rearrangements in chronic B-cell leukemia. Blood 77:1560–1564.PubMedGoogle Scholar
  78. 78.
    Lammie, G. A., Fantl, V., Smith, R., Schuuring, E., Brookes, S., Michalides, R., Dickson, C., Arnold, A., and Peters, G. 1991. D11S287, a putative oncogene on chromosome 11ql3, is amplified and expressed in squamous cell and mammary carcinomas and linked to BCL-1. Oncogene 6:439–444.PubMedGoogle Scholar
  79. 79.
    Jiang, W., Zhang, Y. J., Kahn, S. M., Hollstein, M. C., Santella, R. M., Lu, S. H., Harris, C. C., Montesano, R., and Weinstein, I. B. 1993. Altered expression of the cyclin D1 and retinoblastoma genes in human esophageal cancer. Proc. Natl. Acad. Sci. USA 90:9026–9030.PubMedCrossRefGoogle Scholar
  80. 80.
    Callender, T., el Naggar, A. K., Lee, M. S., Frankenthaler, R., Luna, M. A., and Batsakis, J. G. 1994. PRAD-1 (CCND1)/cyclin D1 oncogene amplification in primary head and neck squamous cell carcinoma. Cancer 74:152–158.PubMedCrossRefGoogle Scholar
  81. 81.
    Wang, T. C., Cardiff, R. D., Zukerberg, L., Lees, E., Arnold, A., and Schmidt, E. V. 1994. Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic mice. Nature 369:669–671.PubMedCrossRefGoogle Scholar
  82. 82.
    Bodrug, S. E., Warner, B. J., Bath, M. L., Lindeman, G. J., Harris, A. W., and Adams, J. M. 1994. Cyclin D1 transgene impedes lymphocyte maturation and collaborates in lymphomagenesis with the myc gene. EMBO J. 13:2124–2130.PubMedGoogle Scholar
  83. 83.
    Lovec, H.I., Grzeschiczek, A., Kowalski, M. B., and Moeroey, T. 1994. Cyclin D1/bcl-1 cooperates with myc genes in the generation of B-cell lymphoma in transgenic mice. EMBO J. 13:3487–3495.PubMedGoogle Scholar
  84. 84.
    Sherr, C. J. 1995. D-type cyclins. Trends Biochem. Sci. 20:187–190.PubMedCrossRefGoogle Scholar
  85. 85.
    Bakhshi, A., Jensen, J. P., Goldman, P., Wright, J. J., McBride, O. W., Epstein, A. L., and Korsmeyer, S. J. 1985. Cloning the chromosomal breakpoint of t(14;18) human lymphomas: Clustering around JH on chromosome 14 and near a transcriptional unit on 18. Cell 41:899–906.PubMedCrossRefGoogle Scholar
  86. 86.
    Ngan, B. Y., Chen Levy, Z., Weiss, L. M., Warnke, R. A., and Cleary, M. L. 1988. Expression in non-Hodgkin’s lymphoma of the bcl-2 protein associated with the t(14,18) chromosomal translocation. N. Engl. J. Med. 318:1638–1644.PubMedCrossRefGoogle Scholar
  87. 87.
    Cleary, M. L., Smith, S. D., and Sklar, J. 1986. Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation. Cell 47:19–28.PubMedCrossRefGoogle Scholar
  88. 88.
    Seto, M., Jaeger, U., Hockett, R. D., Graninger, W., Bennett, S., Goldman, P., and Korsmeyer, S. J. 1988. Alternative promoters and exons, somatic mutation and deregulation of the Bcl-2-Ig fusion gene in lymphoma. EMBO J. 7:123–131.PubMedGoogle Scholar
  89. 89.
    Hengartner, M. O., and Horvitz, H. R. 1994. C. elegans cell survival gene ced-9 encodes a functional homologue of the mammalian proto-oncogene bcl-2, Cell 76:665–676.PubMedCrossRefGoogle Scholar
  90. 90.
    Yuan, J. Y. 1996. Evolution of a genetic pathway of programmed cell death. J. Cell. Biochem. 60:4–11.PubMedCrossRefGoogle Scholar
  91. 91.
    Cory, S. 1995. Regulation of lymphocyte survival by the BCL-2 gene family. Annu. Rev. Immunol. 13:513–543.PubMedCrossRefGoogle Scholar
  92. 92.
    McDonnell, T. J., Deane, N., Platt, F. M., Nunez, G., Jaeger, U., McKearn, J. P., and Korsmeyer, S. J. 1989. bcl-2-immunoglobulin transgenic mice demonstrate extended B cell survival and follicular lympho-proliferation. Cell 57:79–88.PubMedCrossRefGoogle Scholar
  93. 93.
    McDonnell, T. J., and Korsmeyer, S. J. 1991. Progression from lymphoid hyperplasia to high-grade malignant lymphoma in mice transgenic for the t(14; 18). Nature 349:254–256.PubMedCrossRefGoogle Scholar
  94. 94.
    Strasser, A., Harris, A. W., and Cory, S. 1993. E mu-bcl-2 transgene facilitates spontaneous transformation of early pre-B and immunoglobulin-secreting cells but not T cells. Oncogene 8:1–9.PubMedGoogle Scholar
  95. 95.
    McKeithan, T. W., Ohno, H., and Diaz, M. O. Identification of a transcriptional unit adjacent to the breakpoint in the 14;19 translocation of chronic lymphocytic leukemia. Genes Chromosom. Cancer 1:247–255.Google Scholar
  96. 96.
    Kerr, L. D., Duckett, C. S., Wamsley, P., Zhang, Q., Chiao, P., Nabel, G., McKeithan, T. W., Baeuerle, P. A., and Verma, I. M. 1992. The proto-oncogene bcl-3 encodes an I kappa B protein. Genes Dev. 6:2352–2363.PubMedCrossRefGoogle Scholar
  97. 97.
    Wulczyn, F. G., Naumann, M., and Scheidereit, C. 1992. Candidate proto-oncogene bcl-3 encodes a subunit-specific inhibitor of transcription factor NF-kappa B. Nature 358:597–599.PubMedCrossRefGoogle Scholar
  98. 98.
    Zabel, U., Henkel, T., Silva, M. S., and Baeuerle, P. A. 1993. Nuclear uptake control of NF-kappa B by MAD-3, an I kappa B protein present in the nucleus. EMBO J. 12:201–211.PubMedGoogle Scholar
  99. 99.
    Baeuerle, P. A., and Baltimore, D. 1988. I kappa B: A specific inhibitor of the NF-kappa B transcription factor. Science 242:540–546.PubMedCrossRefGoogle Scholar
  100. 100.
    Hatada, E. N., Nieters, A., Wulczyn, F. G., Naumann, M., Meyer, R., Nucifora, G., McKeithan, T. W., and Scheidereit, C. 1992. The ankyrin repeat domains of the NF-kappa B precursor p105 and the protooncogene bcl-3 act as specific inhibitors of NF-kappa B DNA binding. Proc. Natl. Acad. Sci. USA 89:2489–2493.PubMedCrossRefGoogle Scholar
  101. 101.
    Ganchi, P. A., Sun, S. C., Greene, W. C., and Ballard, D. W. 1992. I kappa B/MAD-3 masks the nuclear localization signal of NF-kappa B p65 and requires the transactivation domain to inhibit NF-kappa B p65 DNA binding. Mol. Biol. Cell 3:1339–1352.PubMedGoogle Scholar
  102. 102.
    Nolan, G. P., Fujita, T., Bhatia, K., Huppi, C., Liou, H. C., Scott, M. L., and Baltimore, D. 1993. The bcl-3 proto-oncogene encodes a nuclear I kappa B-like molecule that preferentially interacts with NF-kappa B p50 and p52 in a phosphorylation-dependent manner. Mol. Cell. Biol. 13:3557–3566.PubMedGoogle Scholar
  103. 103.
    Bours, V., Franzoso, G., Azarenko, V., Park, S., Kanno, T., Brown, K., and Siebenlist, U. 1993. The oncoprotein Bcl-3 directly transactivates through kappa B motifs via association with DNA-binding p50B homodimers. Cell 72:729–739.PubMedCrossRefGoogle Scholar
  104. 104.
    Ohno, H., Takimoto, G., and McKeithan, T. W. 1990. The candidate proto-oncogene bcl-3 is related to genes implicated in cell lineage determination and cell cycle control. Cell 60:991–997.PubMedCrossRefGoogle Scholar
  105. 105.
    Fujita, T., Nolan, G. P., Liou, H. C., Scott, M. L., and Baltimore, D. 1993. The candidate proto-oncogene bcl-3 encodes a transcriptional coactivator that activates through NF-kappa B p50 homodimers. Genes Dev 7:1354–1363.PubMedCrossRefGoogle Scholar
  106. 106.
    Bastard, C., Deweindt, C., Kerckaert, J. P., Lenormand, B., Rossi, A., Pezzella, F., Fruchart, C., Duval, C., Monconduit, M., and Tilly, H. 1994. LAZ3 rearrangements in non-Hodgkin’s lymphoma: Correlation with histology, immunophenotype, karyotype, and clinical outcome in 217 patients. Blood 83:2423–2427.PubMedGoogle Scholar
  107. 107.
    Lo Coco, F., Ye, B. H., Lista, F., Corradini, P., Offit, K., Knowles, D. M., Chaganti, R. S., and Dalla Favera, R. 1994. Rearrangements of the BCL6 gene in diffuse large cell non-Hodgkin’s lymphoma. Blood 83:1757–1759.PubMedGoogle Scholar
  108. 108.
    Baron, B. W., Stanger, R. R., Hume, E., Sadhu, A., Mick, R., Kerckaert, J. P., Deweindt, C., Bastard, C., Nucifora, G., Zeleznikle, N., and McKeithan, T. W. 1995. BCL6 encodes a sequence-specific DNA-binding protein. Genes Chromosom. Cancer 13:221–224.PubMedCrossRefGoogle Scholar
  109. 109.
    Ye, B. H., Lista, F., Lo Coco, F., Knowles, D. M., Offit, K., Chaganti, R. S., and Dalla Favera, R. 1993. Alterations of a zinc finger-encoding gene, BCL-6, in diffuse large-cell lymphoma. Science 262:747–750.PubMedCrossRefGoogle Scholar
  110. 110.
    Zollman, S., Godt, D., Prive, G. G., Couderc, J. L., and Laski, F. A. 1994. The BTB domain, found primarily in zinc finger proteins, defines an evolutionarily conserved family that includes several developmentally regulated genes in Drosophila. Proc. Natl. Acad. Sci. USA 91:10717–10721.PubMedCrossRefGoogle Scholar
  111. 111.
    Kawamata, N., Miki, T., Fukuda, T., Hirosawa, S., and Aoki, N. 1994. The organization of the BCL6 gene. Leukemia 8:1327–1330.PubMedGoogle Scholar
  112. 112.
    Kerckaert, J. P., Deweindt, C., Tilly, H., Quief, S., Lecocq, G., and Bastard, C. 1993. LAZ3, a novel zinc-finger encoding gene, is disrupted by recurring chromosome 3q27 translocations in human lymphomas. Nat. Genet. 5:66–70.PubMedCrossRefGoogle Scholar
  113. 113.
    Bastard, C., Deweindt, C., Quiet, S., Dallery, E., Galieguezouitina, S., Dhooghe, M. C., Tilly, H., and Kerckaert, J. P. 1994. Mechanisms of LAZ3/BCL6 deregulation in non-Hodgkin’s-lymphoma (NHL). Blood 84:A440.Google Scholar
  114. 114.
    Kawamata, N., Miki, T., Ohashi, K., Hirosawa, S., and Aoki, N. 1994. Recognition DNA-sequence of a novel putative transcription factor, BCL6. Blood 84:A40.Google Scholar
  115. 115.
    Zani, V. J., Asou, N., Jadayel, D., Heward, J. M., Shipley, J., Nacheva, E., Takasuki, K., Catovsky, D., and Dyer, M. J. 1996. Molecular cloning of complex chromosomal translocation t(8;14;12)(q24.1;q32.3;q24.1) in a Burkitt lymphoma cell line defines a new gene (BCL7A) with homology to caldesmon. Blood 87:3124–3134.PubMedGoogle Scholar
  116. 116.
    Yamashiro, S., Yoshida, K., Yamakita, Y., and Matsumura, F. 1994. Caldesmon: Possible functions in microfilament reorganization during mitosis and cell transformation. Adv. Exp. Med. Biol. 358:113–122.PubMedGoogle Scholar
  117. 117.
    Matsumura, F., and Yamashiro, S. 1993. Caldesmon. Curr. Opin. Cell. Biol. 5:70–76.PubMedCrossRefGoogle Scholar
  118. 118.
    Meeker, T. C., Hardy, D., Willman, C., Hogan, T., and Abrams, J. 1990. Activation of the interleukin-3 gene by chromosome translocation in acute lymphocytic leukemia with eosinophilia. Blood 76:285–289.PubMedGoogle Scholar
  119. 119.
    Grimaldi, J. C., and Meeker, T. C. 1989. The t(5;14) chromosomal translocation in a case of acute lymphocytic leukemia joins the interleukin-3 gene to the immunoglobulin heavy chain gene. Blood 73:2081–2085.PubMedGoogle Scholar
  120. 120.
    Erikson, J., Nishikura, K., ar Rushdi, A., Finan, J., Emanuel, B., Lenoir, G., Nowell, P. C., and Croce, C. M. 1983. Translocation of an immunoglobulin kappa locus to a region 3’ of an unrearranged c-myc oncogene enhances c-myc transcription. Proc. Natl. Acad. Sci. USA 80:7581–7585.PubMedCrossRefGoogle Scholar
  121. 121.
    Croce, C. M., and Nowell, P. C. 1985. Molecular basis of human B cell neoplasia. Blood 65:1–7.PubMedGoogle Scholar
  122. 122.
    Erikson, J., ar Rushdi, A., Drwinga, H. L., Nowell, P. C, and Croce, C. M. 1983. Transcriptional activation of the translocated c-myc oncogene in Burkitt lymphoma. Proc. Natl. Acad. Sci. USA 80:820–824.PubMedCrossRefGoogle Scholar
  123. 123.
    Adams, J. M., Harris, A. W., Pinkert, C. A., Corcoran, L. M., Alexander, W. S., Cory, S., Palmiter, R. D., and Brinster, R. L. 1985. The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice. Nature 318:533–538.PubMedCrossRefGoogle Scholar
  124. 124.
    Langdon, W. Y., Harris, A. W., Cory, S., and Adams, J. M. 1986. The c-myc oncogene perturbs B lymphocyte development in E-mu-myc transgenic mice. Cell 47:11–18.PubMedCrossRefGoogle Scholar
  125. 125.
    Nussenzweig, M. C., Schmidt, E. V., Shaw, A. C., Sinn, E., Campos Torres, J., Mathey Prevot, B., Pattengale, P. K., and Leder, P. 1988. A human immunoglobulin gene reduces the incidence of lymphomas in c-Myc-bearing transgenic mice. Nature 336:446–450.PubMedCrossRefGoogle Scholar
  126. 126.
    Strasser, A., Harris, A. W., Bath, M. L., and Cory, S. 1990. Novel primitive lymphoid tumours induced in transgenic mice by cooperation between myc and bcl-2. Nature 348:331–333.PubMedCrossRefGoogle Scholar
  127. 127.
    Spanopoulou, E., Early, A., Elliott, J., Crispe, N., Ladyman, H., Ritter, M., Watt, S., Grosveld, F., and Kioussis, D. 1989. Complex lymphoid and epithelial thymic tumours in Thy l-myc transgenic mice. Nature 342:185–189.PubMedCrossRefGoogle Scholar
  128. 128.
    Meichle, A., Philipp, A., and Eilers, M. 1992. The functions of Myc proteins. Biochim. Biophys. Acta 1114:129–146.PubMedGoogle Scholar
  129. 129.
    Neri, A., Chang, C. C., Lombardi, L., Salina, M., Corradini, P., Maiolo, A. T., Chaganti, R. S., and Dalla Favera, R. 1991. B cell lymphoma-associated chromosomal translocation involves candidate oncogene lyt-10. homologous to NF-kappa B p50. Cell 67:1075–1087.PubMedCrossRefGoogle Scholar
  130. 130.
    Fracchiolla, N. S., Lombardi, L., Salina, M., Migliazza, A., Baldini, L., Berti, E., Cro, L., Polli, E., Maiolo, A. T., and Neri, A. 1993. Structural alterations of the NF-kappa B transcription factor lyt-10 in lymphoid malignancies. Oncogene 8:2839–2845.PubMedGoogle Scholar
  131. 131.
    Migliazza, A., Antonacci, R., Fracchiolla, N. S., Ciana, P., and Neri, A. 1994. Heterogeneous chromosomal-aberrations generate 3’ truncations of the NFKB2/lyt-10 gene in lymphoid malignancies. Blood 84:3850–3860.PubMedGoogle Scholar
  132. 132.
    Chang, C. C., Zhang, J., Lombardi, L., Neri, A., and Dalla Favera, R. 1995. Rearranged NFKB-2 genes in lymphoid neoplasms code for constitutively active nuclear transactivators. Mol. Cell. Biol. 15:5180–5187.PubMedGoogle Scholar
  133. 133.
    Chang, C. C., Zhang, J., Lombardi, L., Neri, A., and Dalla Favera, R. 1994. Mechanism of expression and role in transcriptional control of the proto-oncogene NFKB-2/LYT-10. Oncogene 9:923–933.PubMedGoogle Scholar
  134. 134.
    Fan, C. M., and Maniatis, T. 1991. Generation of p50 subunit of NF-kappa B by processing of pl05 through an ATP-dependent pathway. Nature 354:395–398.PubMedCrossRefGoogle Scholar
  135. 135.
    Mercurio, F., DiDonato, J. A., Rosette, C., and Karin, M. 1993. pl05 and p98 precursor proteins play an active role in NF-kappa B-mediated signal transduction. Genes Dev. 7:705–718.PubMedCrossRefGoogle Scholar
  136. 136.
    Liptay, S., Schmid, R. M., Nabel, E. G., and Nabel, G. J. 1994. Transcriptional regulation of NF-kappa B2: Evidence for kappa B-mediated positive and negative autoregulation. Mol. Cell. Biol. 14:7695–7703.PubMedGoogle Scholar
  137. 137.
    Bours, V., Burd, P. R., Brown, K., Villalobos, J., Park, S., Ryseck, R. P., Bravo, R., Kelly, K., and Siebenlist, U. 1992. A novel mitogen-inducible gene product related to p50/p105-NF-kappa B participates in transactivation through a kappa B site. Mol. Cell. Biol. 12:685–695.PubMedGoogle Scholar
  138. 138.
    Baeuerle, P. A., and Henkel, T. 1994. Function and activation of NF-kappa B in the immune system. Annu. Rev. Immunol. 12:141–179.PubMedGoogle Scholar
  139. 139.
    Schmid, R. M., Perkins, N. D., Duckett, C. S., Andrews, P. C., and Nabel, G. J. 1991. Cloning of an NF-kappa B subunit which stimulates HIV transcription in synergy with p65. Nature 352:733–736.PubMedCrossRefGoogle Scholar
  140. 140.
    Lombardi, L., Ciana, P., Cappellini, C., Trecca, D., Guerrini, L., Migliazza, A., Maiolo, A. T., and Neri, A. 1995. Structural and functional characterization of the promoter regions of the NFKB2 gene. Nucleic Acids Res. 23:2328–2336.PubMedCrossRefGoogle Scholar
  141. 141.
    Hirama, T., and Koeffler, H. P. 1995. Role of the cyclin-dependent kinase inhibitors in the development of cancer. Blood 86:841–854.PubMedGoogle Scholar
  142. 142.
    Quesnel, B., Preudhomme, C., Philippe, N., Vanrumbeke, M., Dervite, I., Lai, J. L., Bauters, F., Wattel, E., and Fenaux, P. 1995. P16 gene homozygous deletions in acute lymphoblastic-leukemia. Blood 85:657–663.PubMedGoogle Scholar
  143. 143.
    Hebert, J., Cayuela, J. M., Berkeley, J., and Sigaux, F. 1994. Candidate tumor-suppressor genes MTS1 (p16INK4A) and MTS2 (p15INK4B) display frequent homozygous deletions in primary cells from T-but not from B-cell lineage acute lymphoblastic leukemias. Blood 84:4038–4044.PubMedGoogle Scholar
  144. 144.
    Takeuchi, S., Bartram, C. R., Seriu, T., Miller, C. W., Tobler, A., Janssen, J. W., Reiter, A., Ludwig, W. D., Zimmermann, M., Schwaller, J., Lee, E., Miyoshi, I., and Koeffier, H. P. 1995. Analysis of a family of cyclin-dependent kinase inhibitors: p15/MTS2/INK4B, p16/MTS1/INK4A, and p18 genes in acute lymphoblastic leukemia of childhood. Blood 86:755–760.PubMedGoogle Scholar
  145. 145.
    Serrano, M., Hannon, G. J., and Beach, D. 1993. A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature 366:704–707.PubMedCrossRefGoogle Scholar
  146. 146.
    Yang, R., Gombart, A. F., Serrano, M., and Koeffler, H. P. 1995. Mutalional effects on the p16INK4a tumor suppressor protein. Cancer Res. 55:2503–2506.PubMedGoogle Scholar
  147. 147.
    Jiang, P., Stone, S., Wagner, R., Wang, S., Dayananth, P., Kozak, C. A., Wold, B., and Kamb, A. 1995. Comparative analysis of Homo sapiens and Mus musculus cyclin-dependent kinase (CDK) inhibitor genes p16 (MTS1) and p15 (MTS2). J. Mol. Evol. 41:795–802.PubMedCrossRefGoogle Scholar
  148. 148.
    Hartwell, L. H., and Kastan, M. B. 1994. Cell cycle control and cancer. Science 266:1821–1828.PubMedCrossRefGoogle Scholar
  149. 149.
    Rosenberg, C. L., Wong, E., Petty, E. M., Bale, A. E., Tsujimoto, Y., Harris, N. L., and Arnold, A. 1991. PRAD1, a candidate BCL1 oncogene: Mapping and expression in centrocytic lymphoma. Proc. Natl. Acad. Sci. USA 88:9638–9642.PubMedCrossRefGoogle Scholar

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