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BCL-6

Rearrangement and Mutation in Lymphoma

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Lymphoma

Part of the book series: Methods in Molecular Medicine™ ((MIMM,volume 115))

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Abstract

BCL-6 is a zinc finger transcription factor that is highly expressed in normal germinal center B-cells. Its function is to prevent differentiation and apoptosis and allow growth. BCL-6 also is expressed in various lymphoproliferative conditions, for example, diffuse large cell lymphoma, Burkitt’s lymphoma, and follicular lymphoma as well as lymphocyte predominant Hodgkin’s disease. Expression also has been demonstrated in some T-cell lymphomas. In diffuse large cell lymphoma, BCL-6 is involved in translocations with a number of different translocation partners but most commonly the immunoglobulin heavy chain locus. The first intron of BCL-6 is heavily mutated, and detailed analysis reveals two “hotspots.” The mutated region appears to be within a transcriptional control region, and there is the potential for alterations to contribute to overexpression of BCL-6. Methods for deoxyribonucleic acid extraction from lymphoma samples and amplification by polymerase chain reaction of the hypermutated intronic region are described.

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References

  1. Ye, B. H., Rao, P. H., Chaganti, R. S., and Dalla-Favera R. (1993) Cloning of bcl-6, the locus involved in chromosome translocations affecting band 3q27 in B-cell lymphoma. Cancer Res. 53, 2732–2735.

    PubMed  CAS  Google Scholar 

  2. Chang, C. C., Ye, B. H., Chaganti, R. S., and Dalla-Favera R. (1996) BCL-6, a POZ/zinc-finger protein, is a sequence-specific transcriptional repressor. Proc. Natl. Acad. Sci. USA 93, 6947–6952.

    Article  PubMed  CAS  Google Scholar 

  3. Niu, H., Ye, B. H., and Dalla-Favera R. (1998) Antigen receptor signaling induces MAP kinase-mediated phosphorylation and degradation of the BCL-6 transcription factor. Genes Dev. 12, 1953–1961.

    Article  PubMed  CAS  Google Scholar 

  4. MacLennan, I., and Gray, D. (1986) Antigen-driven selection of virgin and memory B-cells. Immunol. Rev. 91, 61–85.

    Article  PubMed  CAS  Google Scholar 

  5. Allman, D., Jain, A., Dent, A., Maile, R. R., Selvaggi, T., Kehry, M. R., and Staudt, L. M. (1996) BCL-6 expression during B-cell activation. Blood 87, 5257–5268.

    PubMed  CAS  Google Scholar 

  6. Cattoretti, G., Chang, C. C., Cechova, K., Zhang, J., Ye, B. H., Falini, B., et al. (1995) BCL-6 protein is expressed in germinal-center B-cells. Blood 86, 45–53.

    PubMed  CAS  Google Scholar 

  7. Onizuka, T., Moriyama, M., Yamochi, T., Kuroda, T., Kazama, A., Kanazawa, N., et al. (1995) BCL-6 gene product, a 92-to 98-kD nuclear phosphoprotein, is highly expressed in germinal center B-cells and their neoplastic counterparts. Blood 86, 28–37.

    PubMed  CAS  Google Scholar 

  8. Ye, B. H., Cattoretti, G., Shen, Q., Zhang, J., Hawe, N., de Waard, R., et al. (1997) The BCL-6 proto-oncogene controls germinal-center formation and Th2-type inflammation. Nat. Genet. 16, 161–170.

    Article  PubMed  CAS  Google Scholar 

  9. Dent, A. L., Shaffer, A. L., Yu, X., Allman, D., Staudt, L. M. (1997) Control of inflammation, cytokine expression and germinal center formation by BCL-6. Science 276, 589–592.

    Article  PubMed  CAS  Google Scholar 

  10. Fukuda, T., Yoshida, T., Okada, S., Hatano, M., Miki, T., Ishibashi, K., et al. (1997) Disruption of the Bcl6 gene results in an impaired germinal center formation. J. Exp. Med. 186, 439–448.

    Article  PubMed  CAS  Google Scholar 

  11. Toney, L. M., Cattoretti, G., Graf, J. A., Merghoub, T., Pandolfi, P. P., Dalla-Favera, R., et al. (2000) BCL-6 regulates chemokine gene transcription in macrophages. Nat. Immunol. 1, 214–220.

    Article  PubMed  CAS  Google Scholar 

  12. Reljic, R., Wagner, S. D., Peakman, L. J., and Fearon, D. T. (2000) BCL-6 suppresses STAT3 dependent B-cell terminal differentiation. J. Exp. Med. 192, 1841–1848.

    Article  PubMed  CAS  Google Scholar 

  13. Shvarts, A., Brummelkamp, T. R., Scheeren, F., Koh, E., Daley, G. Q., Spits, H., et al. (2002) A senescence rescue screen identifies BCL6 as an inhibitor of antiproliferative p19(ARF)-p53 signaling. Genes Dev. 16, 681–686.

    Article  PubMed  CAS  Google Scholar 

  14. Dent, A. L., Hu-Li, J., Paul, W. E., Staudt, L. M. (1998) T helper type 2 inflammatory disease in the absence of interleukin 4 and transcription factor STAT6. Proc. Natl. Acad. Sci. USA 95, 13823–13828.

    Article  PubMed  CAS  Google Scholar 

  15. Faris, M., Kokot, N., Stahl, N., and Nel, A. E. (1997) Involvement of Stat3 in interleukin-6-induced IgM production in a human B-cell line. Immunology 90, 350–357.

    Article  PubMed  CAS  Google Scholar 

  16. Skinnider, B. F., Elia, A. J., Gascoyne, R. D., Patterson, B., Trumper, L., Kapp, U., et al. (2002) Signal transducer and activator of transcription 6 is frequently activated in Hodgkin and Reed-Sternberg cells of Hodgkin lymphoma. Blood 99, 618–626.

    Article  PubMed  CAS  Google Scholar 

  17. Harris, M. B., Chang, C. C., Berton, M. T., Danial, N. N., Zhang, J., Kuehner, D., et al. (1999) Transcriptional repression of Stat6-dependent interleukin-4-induced genes by BCL-6: specific regulation of iepsilon transcription and immunoglobulin E switching.. Mol. Cell Biol. 19, 7264–7275.

    PubMed  CAS  Google Scholar 

  18. Shaffer, A. L., Yu, X., He, Y., Boldrick, J., Chan, E. P., and Staudt, L. M. (2000) BCL-6 represses genes that function in lymphocyte differentiation, inflammation, and cell cycle control. Immunity 13, 199–212.

    Article  PubMed  CAS  Google Scholar 

  19. Fearon, D. T., Manders, P., and Wagner, S. D. (2001) Arrested differentiation, the self renewing memory lymphocyte and vaccination. Science 293, 248–250.

    Article  PubMed  CAS  Google Scholar 

  20. Toyama, H., Okada, S., Hatano, M., Takahashi, Y., Takeda, N., Ichii, H., et al.. (2002) Memory B-cells without somatic hypermutation are generated from Bcl6-deficient B-cells. Immunity 17, 329–339.

    Article  PubMed  CAS  Google Scholar 

  21. Levy, D., and Darnell, J. (2002) Signalling: STATS: transcriptional control and biological impact. Nat. Rev. Mol. Cell Biol. 3, 651–662.

    Article  PubMed  CAS  Google Scholar 

  22. Bajalica-Lagerkrantz, S., Piehl, F., Farnebo, F., Larsson, C., and Lagerkrantz, J. (1998) Expression of the BCL-6 gene in the pre-and postnatal mouse. Biochem. Biophys. Res. Commun. 247, 357–360.

    Article  Google Scholar 

  23. Yoshida, T., Fukuda, T., Okabe, S., Hatano, M., Miki, T., Hirosawa, N., Isono, K., and Tokuhisa, T. (1996) The BCL6 gene is predominantly expressed in keratinocytes at their terminal differentiation stage. Biochem. Biophys. Res. Commun. 228, 216–220.

    Article  PubMed  CAS  Google Scholar 

  24. Ye, B. H., Lista, F., Lo Coco, F., Knowles, D. M., Offit, K., Chaganti, R. S., et al. (1993) Alterations of a zinc finger-encoding gene, BCL-6, in diffuse large-cell lymphoma. Science 262, 747–750.

    Article  PubMed  CAS  Google Scholar 

  25. Lo Coco, F., Ye, B. H., Lista, F., Corradini, P., Offit, K., Knowles, D. M., et al. (1994) Rearrangements of the BCL6 gene in diffuse large cell non-Hodgkin’s lymphoma. Blood 83, 1757–1759.

    PubMed  Google Scholar 

  26. Offit, K., Coco, F. L., Louie, D., Parsa, N., Leung, D., Portlock, C., et al.. (1994) Rearrangement of the bcl-6 gene as a prognostic marker in diffuse large-cell lymphoma. N. Engl. J. Med. 331, 74–80.

    Article  PubMed  CAS  Google Scholar 

  27. Skinnider, B. F., Horsman, D. E., Dupuis, B., and Gascoyne, R. D. (1999) Bcl-6 and Bcl-2 protein expression in diffuse large B-cell lymphoma and follicular lymphoma: correlation with 3q27 and 18q21 chromosomal abnormalities. Hum. Pathol. 30, 803–808.

    Article  PubMed  CAS  Google Scholar 

  28. Raible, M. D., Hsi, E. D., and Alkan, S. (1999) Bcl-6 protein expression by follicle center lymphomas. A marker for differentiating follicle center lymphomas from other low-grade lymphoproliferative disorders. Am. J. Clin. Pathol. 112, 101–107.

    PubMed  CAS  Google Scholar 

  29. Dogan, A., Bagdi, E., Munson, P., and Isaacson, P. G. (2000) CD10 and BCL-6 expression in paraffin sections of normal lymphoid tissue and B-cell lymphomas. Am. J. Surg. Pathol. 24, 846–852.

    Article  PubMed  CAS  Google Scholar 

  30. Carbone, A., Gloghini, A., Gaidano, G., Dalla-Favera, R., and Falini B. (1997) BCL-6 protein expression in human peripheral T-cell neoplasms is restricted to CD30+ anaplastic large-cell lymphomas. Blood 90, 2445–2450.

    PubMed  CAS  Google Scholar 

  31. Alizadeh, A. A., Eisen, M. B., Davis, R. E., Ma, C., Lossos, I. S., Rosenwald, A., et al. (2000) Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403, 503–511.

    Article  PubMed  CAS  Google Scholar 

  32. Shipp, M., Ross, K., Tamayo, P., Weng, A., Kutok, J., Aguiar, R., et al. (2002) Diffuse large B-cell lymphoma outcome prediction by gene expression profiling and supervised machine learning. Nat. Med. 8, 68–74.

    Article  PubMed  CAS  Google Scholar 

  33. Rosenwald, A., Wright, G., Chan, W. C., Connors, J. M., Campo, E., Fisher, R. I., et al., and Lymphoma/Leukemia Molecular Profiling Project. (2002) The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N. Engl. J. Med. 346, 1937–1947.

    Article  PubMed  Google Scholar 

  34. Butler, M. P., Iida, S., Capello, D., Rossi, D., Rao, P. H., Nallasivam, P., et al. (2002) Alternative translocation breakpoint cluster region 5′ to BCL-6 in B-cell non-Hodgkin’s lymphoma. Cancer Res. 62, 4089–4094.

    PubMed  CAS  Google Scholar 

  35. Ye, B., Chaganti, S., Chang, C., Niu, H., Corradini, P., Chaganti, R, et al. (1995) Chromosomal translocations cause deregulated BCL6 expression by promoter substitution in B-cell lymphoma. EMBO J. 14, 6209–6217.

    PubMed  CAS  Google Scholar 

  36. Akasaka, H., Akasaka, T., Kurata, M., Ueda, C., Shimizu, A., Uchiyama, T., et al. (2000) Molecular anatomy of BCL6 translocations revealed by long-distance polymerase chain reaction-based assays. Cancer Res. 60, 2335–2341.

    PubMed  CAS  Google Scholar 

  37. Akasaka, T., Ueda, C., Kurata, M., Akasaka, H., Yamabe, H., Uchiyama, T., and Ohno, H. (2000) Nonimmunoglobulin (non-Ig)/BCL6 gene fusion in diffuse large B-cell lymphoma results in worse prognosis than Ig/BCL6. Blood 96, 2907–2909.

    PubMed  CAS  Google Scholar 

  38. Ueda, C., Akasaka, T., Kurata, M., Maesako, Y., Nishikori, M., Ichinohasama, R., et al. (2002) The gene for interleukin-21 receptor is the partner of BCL6 in t(3;16)(q27;p11), which is recurrently observed in diffuse large B-cell lymphoma. Oncogene 21, 368–376.

    Article  PubMed  CAS  Google Scholar 

  39. Chen, W., Itoyama, T., and Chaganti, R. (2001) Splicing factor SRP20 is a novel partner of BCL6 in a t(3;6)(q27;p21) translocation in transformed follicular lymphoma. Genes Chromosomes Cancer 32, 281–284.

    Article  PubMed  CAS  Google Scholar 

  40. Galiegue-Zouitina, S., Quief, S., Hildebrand, M. P., Denis, C., Detourmignies, L., Lai, J. L., et al. (1999) Nonrandom fusion of L-plastin (LCP1) and LAZ3 (BCL6) genes by t(3;13)(q27;q14) chromosome translocation in two cases of B-cell non-Hodgkin lymphoma. Genes Chromosomes Cancer 26, 97–105.

    Article  PubMed  CAS  Google Scholar 

  41. Hosokawa, Y., Maeda, Y., Ichinohasama, R., Miura, I., Taniwaki, M., and Seto, M. (2000) The Ikaros gene, a central regulator of lymphoid differentiation, fuses to the BCL6 gene as a result of t(3;7)(q27;p12) translocation in a patient with diffuse large B-cell lymphoma. Blood 95, 2719–2721.

    PubMed  CAS  Google Scholar 

  42. Yoshida, S., Y. Kaneita, Y. Aoki, M. Seto, S. Mori, and M. Moriyama. (1999) Identification of heterologous translocation partner genes fused to the BCL6 gene in diffuse large B-cell lymphomas: 5′-RACE and LA-PCR analyses of biopsy samples. Oncogene 18, 7994–7999.

    Article  PubMed  CAS  Google Scholar 

  43. Dallery, E., Galiegue-Zouitina, S., Collyn-d’Hooghe, M., Quief, S., Denis, C., Hildebrand, M. P., et al.(1995) TTF, a gene encoding a novel small G protein, fuses to the lymphoma-associated LAZ3 gene by t(3;4) chromosomal translocation. Oncogene 10, 2171–2178.

    PubMed  CAS  Google Scholar 

  44. Galiegue-Zouitina, S., Quief, S., Hildebrand, M.,. Denis, C., Lecocq, G., Collynd’Hooghe, M., et al. (1995) Fusion of the LAZ3/BCL6 and BOB1/OBF1 genes by t(3; 11) (q27; q23) chromosomal translocation. C R Acad. Sci. III 318, 1125–1131.

    PubMed  CAS  Google Scholar 

  45. Xu, W. S., Liang, R. H., and Srivastava, G. (2000) Identification and characterization of BCL6 translocation partner genes in primary gastric high-grade B-cell lymphoma: heat shock protein 89 alpha is a novel fusion partner gene of BCL6. Genes Chromosomes Cancer 27, 69–75.

    Article  PubMed  CAS  Google Scholar 

  46. Kawasaki, C., Ohshim, K., Suzumiya, J., Kanda, M., Tsuchiya, T., Tamura, K., et al. (2001) Rearrangements of bcl-1, bcl-2, bcl-6, and c-myc in diffuse large B-cell lymphomas. Leuk. Lymphoma 42, 1099–1106.

    Article  PubMed  CAS  Google Scholar 

  47. Huang, J., Sanger, W., Greiner, T., Staudt, L. Weisenburger, D., Pickering, D., et al. (2002) The t(14;18) defines a unique subset of diffuse large B-cell lymphoma with a germinal center B-cell gene expression profile. Blood 99, 2285–2290.

    Article  PubMed  CAS  Google Scholar 

  48. Horsman, D. E., McNeil, B. K., Anderson, M., Shenkier, T., and Gascoyne, R. D. (1995) Frequent association of t(3;14) or variant with other lymphoma-specific translocations. Br. J. Haematol. 89, 569–575.

    Article  PubMed  CAS  Google Scholar 

  49. Au, W. Y., Gascoyne, R. D., Viswanatha, D. S., Skinnider, B. F., Connors, J. M., Klasa, R. J., et al. (1999) Concurrent chromosomal alterations at 3q27, 8q24 and 18q21 in B-cell lymphomas. Br. J. Haematol. 105, 437–440.

    Article  PubMed  CAS  Google Scholar 

  50. Berek, C., and Milstein, C. (1987) Mutation drift and repertoire shift in the maturation of the immune response. Immunol. Rev. 96, 23–41.

    Article  PubMed  CAS  Google Scholar 

  51. Wagner, S., and Neuberger, M. (1996) Somatic hypermutation of immunoglobulin genes. Annu. Rev. Immunol. 14, 441–457.

    Article  PubMed  CAS  Google Scholar 

  52. Revy, P., Muto, T., Levy, Y., Geissmann, F., Plebani, A., Sanal, O., et al. (2000) Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2). Cell 102, 565–575.

    Article  PubMed  CAS  Google Scholar 

  53. Muramatsu, M., Kinoshita, K., Fagarasan, S., Yamada, S., Shinkai, Y., and Honjo T. (2000) Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 102, 553–563.

    Article  PubMed  CAS  Google Scholar 

  54. Harris, R. S., Sale, J. E., Petersen-Mahrt, S. K., and Neuberger, M. S. (2002) AID is essential for immunoglobulin V gene conversion in a cultured B-cell line. Curr. Biol. 12, 435–438.

    Article  PubMed  CAS  Google Scholar 

  55. Nagaoka, H., Muramatsu, M., Yamamura, N., Kinoshita, K., and Honjo T. (2002) Activation-induced deaminase (AID)-directed hypermutation in the immunoglobulin Smu region: implication of AID involvement in a common step of class switch recombination and somatic hypermutation. J. Exp. Med. 195, 529–534.

    Article  PubMed  CAS  Google Scholar 

  56. Okazaki, I. M., Kinoshita, K., Muramatsu, M., Yoshikawa, K., and Honjo T. (2002) The AID enzyme induces class switch recombination in fibroblasts. Nature 416, 340–345.

    Article  PubMed  CAS  Google Scholar 

  57. Jacob, J., Kelsoe, G., Rajewsky, K., and Weiss U. (1991) Intraclonal generation of antibody mutants in germinal centers. Nature 354, 389–392.

    Article  PubMed  CAS  Google Scholar 

  58. Pasqualucci, L., Migliazza, A., Fracchiolla, N., William, C., Neri, A., Baldini, L., et al. (1998) BCL-6 mutations in normal germinal center B-cells: evidence of somatic hypermutation acting outside Ig loci. Proc. Natl. Acad. Sci. USA 95, 11816–11821.

    Article  PubMed  CAS  Google Scholar 

  59. Shen, H. M., Peters, A., Baron, B., Zhu, X., and Storb U. (1998) Mutation of BCL-6 gene in normal B-cells by the process of somatic hypermutation of Ig genes. Science 280, 1750–1752.

    Article  PubMed  CAS  Google Scholar 

  60. Pasqualucci, L., Neumeister, P., Goossens, T., Nanjangud, G., Chaganti, R. S., Kuppers, R., et al. (2001) Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas. Nature 412, 341–346.

    Article  PubMed  CAS  Google Scholar 

  61. Nakamura, Y., K. Saito, and S. Furusawa. (1999) Analysis of internal deletions within the BCL6 gene in B-cell non-Hodgkin’s lymphoma. Br. J. Haematol. 105, 274–277.

    PubMed  CAS  Google Scholar 

  62. Gottgens, B., Gilbert, J. G., Barton, L. M., Grafham, D., Rogers, J., Bentley, D. R., et al. (2001) Long-range comparison of human and mouse SCL loci: localized regions of sensitivity to restriction endonucleases correspond precisely with peaks of conserved noncoding sequences. Genome Res. 11, 87–97.

    Article  PubMed  CAS  Google Scholar 

  63. Kikuchi, M., Miki, T., Kumagai, T., Fukuda, T., Kamiyama, R., Miyasaka, N., and Hirosawa, S. (2000) Identification of negative regulatory regions within the first exon and intron of the BCL-6 gene. Oncogene 19, 4941–4945.

    Article  PubMed  CAS  Google Scholar 

  64. Lossos, I., Jacobs, Y., Cleary, M., and Levy, R. (2001) Correspondence re: Akasaka, H. et al. Molecular anatomy of BCL6 translocations revealed by longdistance polymerase chain reaction based assays. Cancer Res. 60, 2335–2341, 2000. Cancer Res. 61, 7363–7364.

    Google Scholar 

  65. Migliazza, A., Martinotti, S., Chen, W., Fusco, C., Ye, B. H., Knowles, D. M., et al. (1995) Frequent somatic hypermutation of the 5′ noncoding region of the BCL6 gene in B-cell lymphoma. Proc. Natl. Acad. Sci. USA 92, 12520–12524.

    Article  PubMed  CAS  Google Scholar 

  66. Capello, D., Vitolo, U., Pasqualucci, L., Quattrone, S., Migliaretti, G., Fassone, L., et al. (2000) Distribution and pattern of BCL-6 mutations throughout the spectrum of B-cell neoplasia. Blood 95, 651–659.

    PubMed  CAS  Google Scholar 

  67. Artiga, M. J., Saez, A. I., Romero, C., Sanchez-Beato, M., Mateo, M. S., Navas, C., et al. (2002) A short mutational hot spot in the first intron of BCL-6 is associated with increased BCL-6 expression and with longer overall survival in large Bcell lymphomas. Am. J. Pathol. 160, 1371–1380.

    Article  PubMed  CAS  Google Scholar 

  68. Lossos, I. S., Levy R. (2000) Mutation analysis of the 5′ noncoding regulatory region of the BCL-6 gene in non-Hodgkin lymphoma: evidence for recurrent mutations and intraclonal heterogeneity. Blood 95, 1400–1405.

    PubMed  CAS  Google Scholar 

  69. Rogozin, I., and N. Kolchanov. (1992) Somatic hypermutagenesis in immunoglobulin genes. I. I. Influence of neighbouring base sequences on mutagenesis. Biochim. Biophys. Acta. 1171, 11–18.

    PubMed  CAS  Google Scholar 

  70. Vitolo, U., Botto, B., Capello, D., Vivenza, D., Zagonel, V., Gloghini, A., et al. (2002) Point mutations of the BCL-6 gene: clinical and prognostic correlation in B-diffuse large cell lymphoma. Leukemia 16, 268–275.

    Article  PubMed  CAS  Google Scholar 

  71. Sahota, S., Davis, Z., Hamblin, T., and Stevenson, F. (2000) Somatic mutation of bcl-6 genes can occur in the absence of V(H) mutations in chronic lymphocytic leukemia. Blood 95, 3534–3540.

    PubMed  CAS  Google Scholar 

  72. Pasqualucci, L., Neri, A., Baldini, L., Dalla-Favera, R., and Migliazza A. (2000) BCL-6 mutations are associated with immunoglobulin variable heavy chain mutations in B-cell chronic lymphocytic leukemia. Cancer Res. 60, 5644–5648.

    PubMed  CAS  Google Scholar 

  73. Seitz, V., Hummel, M., Anagnostopoulos, I., and Stein, H. (2001) Analysis of BCL-6 mutations in classic Hodgkin disease of the B-and T-cell type. Blood 97, 2401–2405.

    Article  PubMed  CAS  Google Scholar 

  74. Wang, X., Li, Z., Naganuma, A., and Ye, B. (2002) Negative autoregulation of BCL-6 is bypassed by genetic alterations in diffuse large B-cell lymphomas. Proc. Natl. Acad. Sci. USA 99, 15018–15023.

    Article  PubMed  CAS  Google Scholar 

  75. Pasqualucci, L., Migliazza, A., Basso, K., Houldsworth, J., Chaganti, R., and Dalla-Favera, R. (2003) Mutations of the BCL-6 proto-oncogene disrupt its negative autoregulation in diffuse large cell lymphoma. Blood 101, 2914–2923.

    Article  PubMed  CAS  Google Scholar 

  76. Lossos, I., and Levy, R. (2000) Higher-grade transformation of follicle center lymphoma is associated withsomatic mutation of the 5′ noncoding regulatory region of the BCL-6 gene. Blood 96, 635–639.

    PubMed  CAS  Google Scholar 

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Acknowledgment

SDW is supported by the Royal Society Rink Research Fellowship.

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Wagner, S.D., Kaeda, J.S. (2005). BCL-6. In: Illidge, T., Johnson, P.W.M. (eds) Lymphoma. Methods in Molecular Medicine™, vol 115. Humana Press. https://doi.org/10.1385/1-59259-936-2:251

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  • DOI: https://doi.org/10.1385/1-59259-936-2:251

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