The Genetic Landscape of Diffuse Large B-Cell Lymphoma

Seminars in Hematology

Volumn 52, Issue 2, 2015, Pages 67-76

  Pasqualucci, Laura ^a   Dalla Favera, Riccardo ^b  

^a NewYork Presbyterian Hospital   (United States)

^b Och Spine at New York Presbyterian Hospitals   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN BINDING PROTEIN; E1A ASSOCIATED P300 PROTEIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; PROTEIN BCL 6; TOLL LIKE RECEPTOR; TRANSCRIPTION FACTOR EZH2;

B LYMPHOCYTE; B LYMPHOCYTE DIFFERENTIATION; BCL6 GENE; CANCER CLASSIFICATION; CANCER GENETICS; CELL COMPARTMENTALIZATION; CREBBP GENE; EP300 GENE; EZH2 GENE; G ALPHA 13 GENE; GENE; GENE MUTATION; GENETIC RECOMBINATION; GERMINAL CENTER; HISTONE MODIFICATION; HUMAN; LARGE CELL LYMPHOMA; LEUKEMOGENESIS; MOLECULAR PATHOLOGY; NONHUMAN; PRIORITY JOURNAL; REVIEW; SOMATIC HYPERMUTATION; TUMOR MICROENVIRONMENT; CELL DIFFERENTIATION; GENETICS; GENOMICS; IMMUNOLOGY; LYMPHOCYTE ACTIVATION; MUTATION; PATHOLOGY;

B-LYMPHOCYTES; CELL DIFFERENTIATION; GENOMICS; HUMANS; LYMPHOCYTE ACTIVATION; LYMPHOMA, LARGE B-CELL, DIFFUSE; MUTATION;

EID: 84925244524     PISSN: 00371963     EISSN: 15328686     Source Type: Journal    
DOI: 10.1053/j.seminhematol.2015.01.005     Document Type: Review

References (71)

1. Swerdlow S.H., Campo E., Harris N.L., et al. WHO classification of tumors of haematopoietic and lymphoid tissues 2008, IARC, Lyon, France. 4th ed.
2. Klein U., Dalla-Favera R. Germinal centres: role in B-cell physiology and malignancy. Nat Rev Immunol 2008, 8(1):22-33.
3. Victora G.D., Nussenzweig M.C. Germinal centers. Ann Rev Immunol 2012, 30:429-457.
4. Calado D.P., Sasaki Y., Godinho S.A., et al. The cell-cycle regulator c-Myc is essential for the formation and maintenance of germinal centers. Nat Immunol 2012, 13(11):1092-1100.
5. Dominguez-Sola D., Victora G.D., Ying C.Y., et al. The proto-oncogene MYC is required for selection in the germinal center and cyclic reentry. Nat Immunol 2012, 13(11):1083-1091.
6. Basso K., Dalla-Favera R. Roles of BCL6 in normal and transformed germinal center B cells. Immunol Rev 2012, 247(1):172-183.
7. Beguelin W., Popovic R., Teater M., et al. EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation. Cancer Cell 2013, 23(5):677-692.
8. Caganova M., Carrisi C., Varano G., et al. Germinal center dysregulation by histone methyltransferase EZH2 promotes lymphomagenesis. J Clin Invest 2013, 123(12):5009-5022.
9. Saito M., Gao J., Basso K., et al. A signaling pathway mediating downregulation of BCL6 in germinal center B cells is blocked by BCL6 gene alterations in B cell lymphoma. Cancer Cell 2007, 12(3):280-292.
10. Alizadeh A.A., Eisen M.B., Davis R.E., et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 2000, 403(6769):503-511.
11. Rosenwald A., Wright G., Leroy K., et al. Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. J Exper Med 2003, 198(6):851-862.
12. Savage K.J., Monti S., Kutok J.L., et al. The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma. Blood 2003, 102(12):3871-3879.
13. Victora G.D., Dominguez-Sola D., Holmes A.B., Deroubaix S., Dalla-Favera R., Nussenzweig M.C. Identification of human germinal center light and dark zone cells and their relationship to human B-cell lymphomas. Blood 2012, 120(11):2240-2248.
14. Lossos I.S., Alizadeh A.A., Eisen M.B., et al. Ongoing immunoglobulin somatic mutation in germinal center B cell-like but not in activated B cell-like diffuse large cell lymphomas. Proc Natl Acad Sci U S A 2000, 97(18):10209-10213.
15. Lenz G., Nagel I., Siebert R., et al. Aberrant immunoglobulin class switch recombination and switch translocations in activated B cell-like diffuse large B cell lymphoma. J Exper Med 2007, 204(3):633-643.
16. Steidl C., Gascoyne R.D. The molecular pathogenesis of primary mediastinal large B-cell lymphoma. Blood 2011, 118(10):2659-2669.
17. Hans C.P., Weisenburger D.D., Greiner T.C., et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 2004, 103(1):275-282.
18. Rosenwald A., Wright G., Chan W.C., et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med 2002, 346(25):1937-1947.
19. Monti S., Savage K.J., Kutok J.L., et al. Molecular profiling of diffuse large B-cell lymphoma identifies robust subtypes including one characterized by host inflammatory response. Blood 2005, 105(5):1851-1861.
20. Muramatsu M., Kinoshita K., Fagarasan S., Yamada S., Shinkai Y., Honjo T. Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 2000, 102(5):553-563.
21. Revy P., Muto T., Levy Y., et al. Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2). Cell 2000, 102(5):565-575.
22. Kuppers R., Dalla-Favera R. Mechanisms of chromosomal translocations in B cell lymphomas. Oncogene 2001, 20(40):5580-5594.
23. Pasqualucci L., Bhagat G., Jankovic M., et al. AID is required for germinal center-derived lymphomagenesis. Nat Genet 2008, 40(1):108-112.
24. Ramiro A.R., Jankovic M., Eisenreich T., et al. AID is required for c-myc/IgH chromosome translocations in vivo. Cell 2004, 118(4):431-438.
25. Pasqualucci L., Neumeister P., Goossens T., et al. Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas. Nature 2001, 412(6844):341-346.
26. Pasqualucci L., Migliazza A., Fracchiolla N., et al. BCL-6 mutations in normal germinal center B cells: evidence of somatic hypermutation acting outside Ig loci. Proc Natl Acad Sci U S A 1998, 95(20):11816-11821.
27. Shen H.M., Peters A., Baron B., Zhu X., Storb U. Mutation of BCL-6 gene in normal B cells by the process of somatic hypermutation of Ig genes. Science 1998, 280(5370):1750-1752.
28. Yamane A., Resch W., Casellas R. Deep-sequencing identification of the genomic targets of the cytidine deaminase AID and its cofactor RPA in B lymphocytes. Nat Immunol 2011, 12(1):62-69.
29. Liu M., Duke J.L., Richter D.J., et al. Two levels of protection for the B cell genome during somatic hypermutation. Nature 2008, 451(7180):841-845.
30. Khodabakhshi A.H., Morin R.D., Fejes A.P., et al. Recurrent targets of aberrant somatic hypermutation in lymphoma. Oncotarget 2012, 3(11):1308-1319.
31. Lawrence M.S., Stojanov P., Polak P., et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 2013, 499(7457):214-218.
32. Lohr J.G., Stojanov P., Lawrence M.S., et al. Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing. Proc Natl Acad Sci U S A 2012, 109(10):3879-3884.
33. Morin R.D., Mendez-Lago M., Mungall A.J., et al. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature 2011, 476(7360):298-303.
34. Pasqualucci L., Trifonov V., Fabbri G., et al. Analysis of the coding genome of diffuse large B-cell lymphoma. Nat Genet 2011, 43(9):830-837.
35. Goodman R.H., Smolik S. CBP/p300 in cell growth, transformation, and development. Genes Devel 2000, 14(13):1553-1577.
36. Pasqualucci L., Dominguez-Sola D., Chiarenza A., et al. Inactivating mutations of acetyltransferase genes in B-cell lymphoma. Nature 2011, 471(7337):189-195.
37. Bereshchenko O.R., Gu W., Dalla-Favera R. Acetylation inactivates the transcriptional repressor BCL6. Nat Genet 2002, 32(4):606-613.
38. Phan R.T., Dalla-Favera R. The BCL6 proto-oncogene suppresses p53 expression in germinal-centre B cells. Nature 2004, 432(7017):635-639.
39. Pasqualucci L., Khiabanian H., Fangazio M., et al. Genetics of follicular lymphoma transformation. Cell Rep 2014, 6(1):130-140.
40. Green M.R., Gentles A.J., Nair R.V., et al. Hierarchy in somatic mutations arising during genomic evolution and progression of follicular lymphoma. Blood 2013, 121(9):1604-1611.
41. Iqbal J., Greiner T.C., Patel K., et al. Distinctive patterns of BCL6 molecular alterations and their functional consequences in different subgroups of diffuse large B-cell lymphoma. Leukemia 2007, 21(11):2332-2343.
42. Ye B.H., Lista F., Lo Coco F., et al. Alterations of a zinc finger-encoding gene, BCL-6, in diffuse large-cell lymphoma. Science 1993, 262(5134):747-750.
43. Parekh S., Polo J.M., Shaknovich R., et al. BCL6 programs lymphoma cells for survival and differentiation through distinct biochemical mechanisms. Blood 2007, 110(6):2067-2074.
44. Pasqualucci L., Migliazza A., Basso K., Houldsworth J., Chaganti R.S., Dalla-Favera R. Mutations of the BCL6 proto-oncogene disrupt its negative autoregulation in diffuse large B-cell lymphoma. Blood 2003, 101(8):2914-2923.
45. Wang X., Li Z., Naganuma A., Ye B.H. Negative autoregulation of BCL-6 is bypassed by genetic alterations in diffuse large B cell lymphomas. Proc Natl Acad Sci U S A 2002, 99(23):15018-15023.
46. Ying C.Y., Dominguez-Sola D., Fabi M., et al. MEF2B mutations lead to deregulated expression of the oncogene BCL6 in diffuse large B cell lymphoma. Nat Immunol 2013, 14(10):1084-1092.
47. Duan S., Cermak L., Pagan J.K., et al. FBXO11 targets BCL6 for degradation and is inactivated in diffuse large B-cell lymphomas. Nature 2012, 481(7379):90-93.
48. Cattoretti G., Pasqualucci L., Ballon G., et al. Deregulated BCL6 expression recapitulates the pathogenesis of human diffuse large B cell lymphomas in mice. Cancer Cell 2005, 7(5):445-455.
49. Challa-Malladi M., Lieu Y.K., Califano O., et al. Combined genetic inactivation of beta2-Microglobulin and CD58 reveals frequent escape from immune recognition in diffuse large B cell lymphoma. Cancer Cell 2011, 20(6):728-740.
50. Cresswell P., Ackerman A.L., Giodini A., Peaper D.R., Wearsch P.A. Mechanisms of MHC class I-restricted antigen processing and cross-presentation. Immunol Rev 2005, 207:145-157.
51. Monti S., Chapuy B., Takeyama K., et al. Integrative analysis reveals an outcome-associated and targetable pattern of p53 and cell cycle deregulation in diffuse large B cell lymphoma. Cancer Cell 2012, 22(3):359-372.
52. Trinh D.L., Scott D.W., Morin R.D., et al. Analysis of FOXO1 mutations in diffuse large B-cell lymphoma. Blood 2013, 121(18):3666-3674.
53. Saito M., Novak U., Piovan E., et al. BCL6 suppression of BCL2 via Miz1 and its disruption in diffuse large B cell lymphoma. Proc Natl Acad Sci U S A 2009, 106(27):11294-11299.
54. Lenz G., Wright G.W., Emre N.C., et al. Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathways. Proc Natl Acad Sci U S A 2008, 105(36):13520-13525.
55. Morin R.D., Johnson N.A., Severson T.M., et al. Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. Nat Genet 2010, 42(2):181-185.
56. Yap D.B., Chu J., Berg T., et al. Somatic mutations at EZH2 Y641 act dominantly through a mechanism of selectively altered PRC2 catalytic activity, to increase H3K27 trimethylation. Blood 2011, 117(8):2451-2459.
57. Roschewski M., Staudt L.M., Wilson W.H. Diffuse large B-cell lymphoma-treatment approaches in the molecular era. Nat Rev Clin Oncol 2014, 11(1):12-23.
58. Muppidi J.R., Schmitz R., Green J.A., et al. Loss of signalling via Gα13 in germinal centre B-cell-derived lymphoma. Nature 2014, 516(7530):2548-2552.
59. Davis R.E., Brown K.D., Siebenlist U., Staudt L.M. Constitutive nuclear factor kappaB activity is required for survival of activated B cell-like diffuse large B cell lymphoma cells. J Exper Med 2001, 194(12):1861-1874.
60. Davis R.E., Ngo V.N., Lenz G., et al. Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature 2010, 463(7277):88-92.
61. Thome M.CARMA1 BCL-10 and MALT1 in lymphocyte development and activation. Nat Rev Immunol 2004, 4(5):348-359.
62. Lenz G., Davis R.E., Ngo V.N., et al. Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science 2008, 319(5870):1676-1679.
63. Ngo V.N., Young R.M., Schmitz R., et al. Oncogenically active MYD88 mutations in human lymphoma. Nature 2011, 470(7332):115-119.
64. Compagno M., Lim W.K., Grunn A., et al. Mutations of multiple genes cause deregulation of NF-kappaB in diffuse large B-cell lymphoma. Nature 2009, 459(7247):717-721.
65. Kato M., Sanada M., Kato I., et al. Frequent inactivation of A20 in B-cell lymphomas. Nature 2009, 459(7247):712-716.
66. Boone D.L., Turer E.E., Lee E.G., et al. The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses. Nat Immunol 2004, 5(10):1052-1060.
67. Shapiro-Shelef M., Lin K.I., McHeyzer-Williams L.J., Liao J., McHeyzer-Williams M.G., Calame K. Blimp-1 is required for the formation of immunoglobulin secreting plasma cells and pre-plasma memory B cells. Immunity 2003, 19(4):607-620.
68. Mandelbaum J., Bhagat G., Tang H., et al. BLIMP1 is a tumor suppressor gene frequently disrupted in activated B cell-like diffuse large B cell lymphoma. Cancer Cell 2010, 18(6):568-579.
69. Pasqualucci L., Compagno M., Houldsworth J., et al. Inactivation of the PRDM1/BLIMP1 gene in diffuse large B cell lymphoma. J Exper Med 2006, 203(2):311-317.
70. Tam W., Gomez M., Chadburn A., Lee J.W., Chan W.C., Knowles D.M. Mutational analysis of PRDM1 indicates a tumor-suppressor role in diffuse large B-cell lymphomas. Blood 2006, 107(10):4090-4100.
71. Calado D.P., Zhang B., Srinivasan L., et al. Constitutive canonical NF-kappaB activation cooperates with disruption of BLIMP1 in the pathogenesis of activated B cell-like diffuse large cell lymphoma. Cancer Cell 2010, 18(6):580-589.