Skip to main content
SpringerLink
Log in

Genetics in Lymphomagenesis

  • Chapter
  • First Online:
Neoplastic Diseases of the Blood

  • 2747 Accesses

Abstract

Lymphoproliferative diseases include many different disease entities with distinct cells of origin, pathologies, risk factor profiles, and prognoses. Although lymphomas are grouped traditionally into non-Hodgkin and Hodgkin lymphomas, the WHO classification today separates lymphomas into three main groups, B-cell, T-/NK-cell and Hodgkin lymphomas, where each group includes multiple subtypes. For instance, B-cell lymphomas comprise entities such as follicular lymphomas, diffuse large B-cell lymphomas, chronic lymphocytic leukemia, and lymphoplasmacytic lymphoma/Waldenström macroglobulinemia. The causes of lymphomas are mostly unknown; however, known risk factors include autoimmunity, infections, and heredity. This chapter will focus on familiality, define basic concepts in lymphomagenesis, and discuss important genetic events in specific lymphomas.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 269.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Kristinsson SY, Goldin LR, Bjorkholm M, Koshiol J, Turesson I, Landgren O. Genetic and immune-related factors in the pathogenesis of lymphoproliferative and plasma cell malignancies. Haematologica. 2009;94:1581–9.

    Article  PubMed  Google Scholar 

  2. Goldin LR, Landgren O, McMaster ML, et al. Familial aggregation and heterogeneity of non-Hodgkin lymphoma in population-based samples. Cancer Epidemiol Biomarkers Prev. 2005;14:2402–6.

    Article  PubMed  Google Scholar 

  3. Goldin LR, Pfeiffer RM, Gridley G, et al. Familial aggregation of Hodgkin lymphoma and related tumors. Cancer. 2004;100: 1902–8.

    Article  PubMed  Google Scholar 

  4. Kristinsson SY, Bjorkholm M, Goldin LR, et al. Patterns of hematologic malignancies and solid tumors among 37,838 first-degree relatives of 13,896 patients with multiple myeloma in Sweden. Int J Cancer. 2009;125:2147–50.

    Article  PubMed  CAS  Google Scholar 

  5. Goldin LR, Bjorkholm M, Kristinsson SY, Turesson I, Landgren O. Elevated risk of chronic lymphocytic leukemia and other indolent non-Hodgkin’s lymphomas among relatives of patients with chronic lymphocytic leukemia. Haematologica. 2009;94(5):647–53.

    Article  PubMed  Google Scholar 

  6. Xu Y, Wiernik PH. Systemic lupus erythematosus and B-cell hematologic neoplasm. Lupus. 2001;10:841–50.

    Article  PubMed  CAS  Google Scholar 

  7. Kristinsson SY, Landgren O, Sjoberg J, Turesson I, Bjorkholm M, Goldin LR. Autoimmunity and risk for Hodgkin’s lymphoma by subtype. Haematologica. 2009;94:1468–9.

    Article  PubMed  Google Scholar 

  8. Kristinsson SY, Koshiol J, Bjorkholm M, et al. Immune-related and inflammatory conditions and risk of lymphoplasmacytic lymphoma or Waldenstrom macroglobulinemia. J Natl Cancer Inst. 2010;102:557–67.

    Article  PubMed  CAS  Google Scholar 

  9. Smedby KE, Akerman M, Hildebrand H, Glimelius B, Ekbom A, Askling J. Malignant lymphomas in coeliac disease: evidence of increased risks for lymphoma types other than enteropathy-type T cell lymphoma. Gut. 2005;54:54–9.

    Article  PubMed  CAS  Google Scholar 

  10. Smedby KE, Baecklund E, Askling J. Malignant lymphomas in autoimmunity and inflammation: a review of risks, risk factors, and lymphoma characteristics. Cancer Epidemiol Biomarkers Prev. 2006;15:2069–77.

    Article  PubMed  CAS  Google Scholar 

  11. Smedby KE, Hjalgrim H, Askling J, et al. Autoimmune and chronic inflammatory disorders and risk of non-Hodgkin lymphoma by subtype. J Natl Cancer Inst. 2006;98:51–60.

    Article  PubMed  Google Scholar 

  12. Ferreri AJ, Guidoboni M, Ponzoni M, et al. Evidence for an association between Chlamydia psittaci and ocular adnexal lymphomas. J Natl Cancer Inst. 2004;96:586–94.

    Article  PubMed  Google Scholar 

  13. Wotherspoon AC, Ortiz-Hidalgo C, Falzon MR, Isaacson PG. Helicobacter pylori-associated gastritis and primary B-cell gastric lymphoma. Lancet. 1991;338:1175–6.

    Article  PubMed  CAS  Google Scholar 

  14. Suzuki H, Saito Y, Hibi T. Helicobacter pylori and gastric mucosa-associated lymphoid tissue (MALT) lymphoma: updated review of clinical outcomes and the molecular pathogenesis. Gut Liver. 2009;3:81–7.

    Article  PubMed  CAS  Google Scholar 

  15. Carrillo-Infante C, Abbadessa G, Bagella L, Giordano A. Viral infections as a cause of cancer (review). Int J Oncol. 2007;30:1521–8.

    PubMed  CAS  Google Scholar 

  16. Frohling S, Dohner H. Chromosomal abnormalities in cancer. N Engl J Med. 2008;359:722–34.

    Article  PubMed  CAS  Google Scholar 

  17. Swerdlow SH, Campo E, Harris NL, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: International Agency for Research on Cancer; 2008.

    Google Scholar 

  18. Kuppers R, Dalla-Favera R. Mechanisms of chromosomal translocations in B cell lymphomas. Oncogene. 2001;20:5580–94.

    Article  PubMed  CAS  Google Scholar 

  19. Zenz T, Mertens D, Kuppers R, Dohner H, Stilgenbauer S. From pathogenesis to treatment of chronic lymphocytic leukaemia. Nat Rev Cancer. 2010;10:37–50.

    PubMed  CAS  Google Scholar 

  20. Dohner H, Stilgenbauer S, Benner A, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med. 2000;343:1910–6.

    Article  PubMed  CAS  Google Scholar 

  21. Croce CM. Oncogenes and cancer. N Engl J Med. 2008;358:502–11.

    Article  PubMed  CAS  Google Scholar 

  22. Tsujimoto Y, Gorham J, Cossman J, Jaffe E, Croce CM. The t(14;18) chromosome translocations involved in B-cell neoplasms result from mistakes in VDJ joining. Science. 1985;229:1390–3.

    Article  PubMed  CAS  Google Scholar 

  23. Konopka JB, Watanabe SM, Singer JW, Collins SJ, Witte ON. Cell lines and clinical isolates derived from Ph1-positive chronic myelogenous leukemia patients express c-abl proteins with a common structural alteration. Proc Natl Acad Sci U S A. 1985;82:1810–4.

    Article  PubMed  CAS  Google Scholar 

  24. Finger LR, Harvey RC, Moore RC, Showe LC, Croce CM. A common mechanism of chromosomal translocation in T- and B-cell neoplasia. Science. 1986;234:982–5.

    Article  PubMed  CAS  Google Scholar 

  25. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.

    Article  PubMed  CAS  Google Scholar 

  26. Harfe BD. MicroRNAs in vertebrate development. Curr Opin Genet Dev. 2005;15:410–5.

    Article  PubMed  CAS  Google Scholar 

  27. Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6:857–66.

    Article  PubMed  CAS  Google Scholar 

  28. Calin GA, Dumitru CD, Shimizu M, et al. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2002;99:15524–9.

    Article  PubMed  CAS  Google Scholar 

  29. Altieri A, Bermejo JL, Hemminki K. Familial risk for non-Hodgkin lymphoma and other lymphoproliferative malignancies by histopathologic subtype: the Swedish Family-Cancer Database. Blood. 2005;106:668–72.

    Article  PubMed  CAS  Google Scholar 

  30. Cannon-Albright LA, Thomas A, Goldgar DE, et al. Familiality of cancer in Utah. Cancer Res. 1994;54:2378–85.

    PubMed  CAS  Google Scholar 

  31. Cartwright RA, McKinney PA, O’Brien C, et al. Non-Hodgkin’s lymphoma: case control epidemiological study in Yorkshire. Leuk Res. 1988;12:81–8.

    Article  PubMed  CAS  Google Scholar 

  32. Chatterjee N, Hartge P, Cerhan JR, et al. Risk of non-Hodgkin’s lymphoma and family history of lymphatic, hematologic, and other cancers. Cancer Epidemiol Biomarkers Prev. 2004;13:1415–21.

    PubMed  Google Scholar 

  33. Alexandrescu DT, Garino A, Brown-Balem KA, Wiernik PH. Anticipation in families with Hodgkin’s and non-Hodgkin’s lymphoma in their pedigree. Leuk Lymphoma. 2006;47:2115–27.

    Article  PubMed  Google Scholar 

  34. Vachon CM, Habermann TM, Kurtin PJ, Cerhan JR. Clinical characteristics of familial vs. sporadic non-Hodgkin lymphoma in patients diagnosed at the Mayo Clinic (1986-2000). Leuk Lymphoma. 2004;45:929–35.

    Article  PubMed  Google Scholar 

  35. Goldin L, Björkholm M, Kristinsson SY, Turesson I, Landgren O. Highly increased familial risks for specific lymphoma subtypes. Br J Haematol. 2009;146:91–4.

    Article  PubMed  Google Scholar 

  36. Fine JM, Lambin P, Massari M, Leroux P. Malignant evolution of asymptomatic monoclonal IgM after seven and fifteen years in two siblings of a patient with Waldenstrom’s macroglobulinemia. Acta Med Scand. 1982;211:237–9.

    Article  PubMed  CAS  Google Scholar 

  37. Linet MS, Humphrey RL, Mehl ES, et al. A case-control and family study of Waldenstrom’s macroglobulinemia. Leukemia. 1993;7:1363–9.

    PubMed  CAS  Google Scholar 

  38. McMaster ML, Goldin LR, Bai Y, et al. Genomewide linkage screen for Waldenstrom macroglobulinemia susceptibility loci in high-risk families. Am J Hum Genet. 2006;79:695–701.

    Article  PubMed  CAS  Google Scholar 

  39. Ogmundsdottir HM, Johannesson GM, Sveinsdottir S, et al. Familial macroglobulinaemia: hyperactive B-cells but normal natural killer function. Scand J Immunol. 1994;40:195–200.

    Article  PubMed  CAS  Google Scholar 

  40. Treon SP, Hunter ZR, Aggarwal A, et al. Characterization of familial Waldenstrom’s macroglobulinemia. Ann Oncol. 2006;17:488–94.

    Article  PubMed  CAS  Google Scholar 

  41. Kristinsson SY, Bjorkholm M, Goldin LR, McMaster ML, Turesson I, Landgren O. Risk of lymphoproliferative disorders among first-degree relatives of lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia patients: a population-based study in Sweden. Blood. 2008;112:3052–6.

    Article  PubMed  CAS  Google Scholar 

  42. Goldin LR, Pfeiffer RM, Li X, Hemminki K. Familial risk of lymphoproliferative tumors in families of patients with chronic lymphocytic leukemia: results from the Swedish Family-Cancer Database. Blood. 2004;104:1850–4.

    Article  PubMed  CAS  Google Scholar 

  43. Tsujimoto Y, Cossman J, Jaffe E, Croce CM. Involvement of the bcl-2 gene in human follicular lymphoma. Science. 1985;228:1440–3.

    Article  PubMed  CAS  Google Scholar 

  44. Shih LY, Liang DC. Non-Hodgkin’s lymphomas in Asia. Hematol Oncol Clin North Am. 1991;5:983–1001.

    PubMed  CAS  Google Scholar 

  45. Limpens J, Stad R, Vos C, et al. Lymphoma-associated translocation t(14;18) in blood B cells of normal individuals. Blood. 1995;85:2528–36.

    PubMed  CAS  Google Scholar 

  46. Liu Y, Hernandez AM, Shibata D, Cortopassi GA. BCL2 translocation frequency rises with age in humans. Proc Natl Acad Sci U S A. 1994;91:8910–4.

    Article  PubMed  CAS  Google Scholar 

  47. McDonnell TJ, Korsmeyer SJ. Progression from lymphoid hyperplasia to high-grade malignant lymphoma in mice transgenic for the t(14; 18). Nature. 1991;349:254–6.

    Article  PubMed  CAS  Google Scholar 

  48. Cheung KJ, Delaney A, Ben-Neriah S, et al. High resolution analysis of follicular lymphoma genomes reveals somatic recurrent sites of copy-neutral loss of heterozygosity and copy number alterations that target single genes. Genes Chromosomes Cancer. 2010;49:669–81.

    Article  PubMed  CAS  Google Scholar 

  49. Hoglund M, Sehn L, Connors JM, et al. Identification of cytogenetic subgroups and karyotypic pathways of clonal evolution in ­follicular lymphomas. Genes Chromosomes Cancer. 2004;39:195–204.

    Article  PubMed  Google Scholar 

  50. Bende RJ, Smit LA, van Noesel CJ. Molecular pathways in follicular lymphoma. Leukemia. 2007;21:18–29.

    Article  PubMed  CAS  Google Scholar 

  51. Skibola CF, Bracci PM, Halperin E, et al. Genetic variants at 6p21.33 are associated with susceptibility to follicular lymphoma. Nat Genet. 2009;41:873–5.

    Article  PubMed  CAS  Google Scholar 

  52. Wang SS, Abdou AM, Morton LM, et al. Human leukocyte antigen class I and II alleles in non-Hodgkin lymphoma etiology. Blood. 2010;115:4820–3.

    Article  PubMed  CAS  Google Scholar 

  53. Conde L, Halperin E, Akers NK, et al. Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32. Nat Genet. 2010;42:661–4.

    Article  PubMed  CAS  Google Scholar 

  54. Thelander EF, Rosenquist R. Molecular genetic characterization reveals new subsets of mantle cell lymphoma. Leuk Lymphoma. 2008;49:1042–9.

    Article  PubMed  CAS  Google Scholar 

  55. Sander B, Flygare J, Porwit-Macdonald A, et al. Mantle cell lymphomas with low levels of cyclin D1 long mRNA transcripts are highly proliferative and can be discriminated by elevated cyclin A2 and cyclin B1. Int J Cancer. 2005;117:418–30.

    Article  PubMed  CAS  Google Scholar 

  56. Bertoni F, Zucca E, Cotter FE. Molecular basis of mantle cell lymphoma. Br J Haematol. 2004;124:130–40.

    Article  PubMed  CAS  Google Scholar 

  57. Bodrug SE, Warner BJ, Bath ML, Lindeman GJ, Harris AW, Adams JM. Cyclin D1 transgene impedes lymphocyte maturation and collaborates in lymphomagenesis with the myc gene. EMBO J. 1994;13:2124–30.

    PubMed  CAS  Google Scholar 

  58. Lovec H, Grzeschiczek A, Kowalski MB, Moroy T. Cyclin D1/bcl-1 cooperates with myc genes in the generation of B-cell lymphoma in transgenic mice. EMBO J. 1994;13:3487–95.

    PubMed  CAS  Google Scholar 

  59. Jares P, Colomer D, Campo E. Genetic and molecular pathogenesis of mantle cell lymphoma: perspectives for new targeted therapeutics. Nat Rev Cancer. 2007;7:750–62.

    Article  PubMed  CAS  Google Scholar 

  60. Hartmann EM, Campo E, Wright G, et al. Pathway discovery in mantle cell lymphoma by integrated analysis of high resolution gene expression and copy number profiling. Blood. 2010;116(6):953–61.

    Article  PubMed  CAS  Google Scholar 

  61. Schaffner C, Idler I, Stilgenbauer S, Dohner H, Lichter P. Mantle cell lymphoma is characterized by inactivation of the ATM gene. Proc Natl Acad Sci U S A. 2000;97:2773–8.

    Article  PubMed  CAS  Google Scholar 

  62. Rosenwald A, Wright G, Wiestner A, et al. The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma. Cancer Cell. 2003;3:185–97.

    Article  PubMed  CAS  Google Scholar 

  63. Offit K, Parsa NZ, Filippa D, Jhanwar SC, Chaganti RS. t(9;14)(p13;q32) denotes a subset of low-grade non-Hodgkin’s lymphoma with plasmacytoid differentiation. Blood. 1992;80:2594–9.

    PubMed  CAS  Google Scholar 

  64. Iida S, Rao PH, Nallasivam P, et al. The t(9;14)(p13;q32) chromosomal translocation associated with lymphoplasmacytoid lymphoma involves the PAX-5 gene. Blood. 1996;88:4110–7.

    PubMed  CAS  Google Scholar 

  65. Buckley PG, Walsh SH, Laurell A, et al. Genome-wide microarray-based comparative genomic hybridization analysis of lymphoplasmacytic lymphomas reveals heterogeneous aberrations. Leuk Lymphoma. 2009;50:1528–34.

    Article  PubMed  CAS  Google Scholar 

  66. Schop RF, Kuehl WM, Van Wier SA, et al. Waldenstrom macroglobulinemia neoplastic cells lack immunoglobulin heavy chain locus translocations but have frequent 6q deletions. Blood. 2002;100:2996–3001.

    Article  PubMed  CAS  Google Scholar 

  67. Braggio E, Keats JJ, Leleu X, et al. High-resolution genomic ­analysis in Waldenstrom’s macroglobulinemia identifies disease-specific and common abnormalities with marginal zone lymphomas. Clin Lymphoma Myeloma. 2009;9:39–42.

    Article  PubMed  CAS  Google Scholar 

  68. Rosenwald A, Wright G, Chan WC, et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:1937–47.

    Article  PubMed  Google Scholar 

  69. Alizadeh AA, Eisen MB, Davis RE, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000;403:503–11.

    Article  PubMed  CAS  Google Scholar 

  70. Kramer MH, Hermans J, Wijburg E, et al. Clinical relevance of BCL2, BCL6, and MYC rearrangements in diffuse large B-cell lymphoma. Blood. 1998;92:3152–62.

    PubMed  CAS  Google Scholar 

  71. Gascoyne RD, Adomat SA, Krajewski S, et al. Prognostic significance of Bcl-2 protein expression and Bcl-2 gene rearrangement in diffuse aggressive non-Hodgkin’s lymphoma. Blood. 1997;90:244–51.

    PubMed  CAS  Google Scholar 

  72. Offit K, Koduru PR, Hollis R, et al. 18q21 rearrangement in diffuse large cell lymphoma: incidence and clinical significance. Br J Haematol. 1989;72:178–83.

    Article  PubMed  CAS  Google Scholar 

  73. Iqbal J, Sanger WG, Horsman DE, et al. BCL2 translocation defines a unique tumor subset within the germinal center B-cell-like diffuse large B-cell lymphoma. Am J Pathol. 2004;165:159–66.

    Article  PubMed  CAS  Google Scholar 

  74. Mounier N, Briere J, Gisselbrecht C, et al. Rituximab plus CHOP (R-CHOP) overcomes bcl-2–associated resistance to chemotherapy in elderly patients with diffuse large B-cell lymphoma (DLBCL). Blood. 2003;101:4279–84.

    Article  PubMed  CAS  Google Scholar 

  75. Iqbal J, Greiner TC, 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;21:2332–43.

    Article  PubMed  CAS  Google Scholar 

  76. Ohno H. Pathogenetic and clinical implications of non-immunoglobulin; BCL6 translocations in B-cell non-Hodgkin’s lymphoma. J Clin Exp Hematop. 2006;46:43–53.

    Article  PubMed  Google Scholar 

  77. Akasaka T, Akasaka H, Ueda C, et al. Molecular and clinical features of non-Burkitt’s, diffuse large-cell lymphoma of B-cell type associated with the c-MYC/immunoglobulin heavy-chain fusion gene. J Clin Oncol. 2000;18:510–18.

    PubMed  CAS  Google Scholar 

  78. Yoon SO, Jeon YK, Paik JH, et al. MYC translocation and an increased copy number predict poor prognosis in adult diffuse large B-cell lymphoma (DLBCL), especially in germinal centre-like B cell (GCB) type. Histopathology. 2008;53:205–17.

    Article  PubMed  CAS  Google Scholar 

  79. Houldsworth J, Olshen AB, Cattoretti G, et al. Relationship between REL amplification, REL function, and clinical and biologic features in diffuse large B-cell lymphomas. Blood. 2004;103:1862–8.

    Article  PubMed  CAS  Google Scholar 

  80. Milhollen MA, Traore T, Adams-Duffy J, et al. MLN4924, a NEDD8-activating enzyme inhibitor, is active in diffuse large B-cell lymphoma models: rationale for treatment of NF-{kappa}B-dependent lymphoma. Blood. 2010;116:1515–23.

    Article  PubMed  CAS  Google Scholar 

  81. Davis RE, Brown KD, Siebenlist U, Staudt LM. Constitutive nuclear factor kappaB activity is required for survival of activated B cell-like diffuse large B cell lymphoma cells. J Exp Med. 2001;194:1861–74.

    Article  PubMed  CAS  Google Scholar 

  82. Pasqualucci L, Compagno M, Houldsworth J, et al. Inactivation of the PRDM1/BLIMP1 gene in diffuse large B cell lymphoma. J Exp Med. 2006;203:311–7.

    Article  PubMed  CAS  Google Scholar 

  83. Bea S, Zettl A, Wright G, et al. Diffuse large B-cell lymphoma subgroups have distinct genetic profiles that influence tumor biology and improve gene-expression-based survival prediction. Blood. 2005;106:3183–90.

    Article  PubMed  CAS  Google Scholar 

  84. Skibola CF, Bracci PM, Nieters A, et al. Tumor necrosis factor (TNF) and lymphotoxin-alpha (LTA) polymorphisms and risk of non-Hodgkin lymphoma in the InterLymph Consortium. Am J Epidemiol. 2010;171:267–76.

    Article  PubMed  Google Scholar 

  85. Taub R, Kirsch I, Morton C, et al. Translocation of the c-myc gene into the immunoglobulin heavy chain locus in human Burkitt ­lymphoma and murine plasmacytoma cells. Proc Natl Acad Sci U S A. 1982;79:7837–41.

    Article  PubMed  CAS  Google Scholar 

  86. Pelicci PG, Knowles 2nd DM, Magrath I, Dalla-Favera R. Chromosomal breakpoints and structural alterations of the c-myc locus differ in endemic and sporadic forms of Burkitt lymphoma. Proc Natl Acad Sci U S A. 1986;83:2984–8.

    Article  PubMed  CAS  Google Scholar 

  87. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663–76.

    Article  PubMed  CAS  Google Scholar 

  88. Dang CV, O’Donnell KA, Zeller KI, Nguyen T, Osthus RC, Li F. The c-Myc target gene network. Semin Cancer Biol. 2006;16:253–64.

    Article  PubMed  CAS  Google Scholar 

  89. Vose J, Armitage J, Weisenburger D. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol. 2008;26:4124–30.

    Article  PubMed  Google Scholar 

  90. Thorns C, Bastian B, Pinkel D, et al. Chromosomal aberrations in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma unspecified: A matrix-based CGH approach. Genes Chromosomes Cancer. 2007;46:37–44.

    Article  PubMed  CAS  Google Scholar 

  91. Nelson M, Horsman DE, Weisenburger DD, et al. Cytogenetic abnormalities and clinical correlations in peripheral T-cell lymphoma. Br J Haematol. 2008;141:461–9.

    Article  PubMed  CAS  Google Scholar 

  92. Dogan A, Attygalle AD, Kyriakou C. Angioimmunoblastic T-cell lymphoma. Br J Haematol. 2003;121:681–91.

    Article  PubMed  Google Scholar 

  93. de Leval L, Bisig B, Thielen C, Boniver J, Gaulard P. Molecular classification of T-cell lymphomas. Crit Rev Oncol Hematol. 2009;72:125–43.

    Article  PubMed  Google Scholar 

  94. Schlegelberger B, Zwingers T, Hohenadel K, et al. Significance of cytogenetic findings for the clinical outcome in patients with T-cell lymphoma of angioimmunoblastic lymphadenopathy type. J Clin Oncol. 1996;14:593–9.

    PubMed  CAS  Google Scholar 

  95. Morris SW, Kirstein MN, Valentine MB, et al. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin’s lymphoma. Science. 1994;263:1281–4.

    Article  PubMed  CAS  Google Scholar 

  96. Mason DY, Bastard C, Rimokh R, et al. CD30-positive large cell lymphomas (‘Ki-1 lymphoma’) are associated with a chromosomal translocation involving 5q35. Br J Haematol. 1990;74:161–8.

    Article  PubMed  CAS  Google Scholar 

  97. Amin HM, Lai R. Pathobiology of ALK  +  anaplastic large-cell lymphoma. Blood. 2007;110:2259–67.

    Article  PubMed  CAS  Google Scholar 

  98. Salaverria I, Bea S, Lopez-Guillermo A, et al. Genomic profiling reveals different genetic aberrations in systemic ALK-positive and ALK-negative anaplastic large cell lymphomas. Br J Haematol. 2008;140:516–26.

    Article  PubMed  Google Scholar 

  99. Lamant L, de Reynies A, Duplantier MM, et al. Gene-expression profiling of systemic anaplastic large-cell lymphoma reveals differences based on ALK status and two distinct morphologic ALK  +  subtypes. Blood. 2007;109:2156–64.

    Article  PubMed  CAS  Google Scholar 

  100. Zettl A, Rudiger T, Konrad MA, et al. Genomic profiling of peripheral T-cell lymphoma, unspecified, and anaplastic large T-cell lymphoma delineates novel recurrent chromosomal alterations. Am J Pathol. 2004;164:1837–48.

    Article  PubMed  CAS  Google Scholar 

  101. Goldin LR, Ishibe N, Sgambati M, et al. A genome scan of 18 families with chronic lymphocytic leukaemia. Br J Haematol. 2003;121:866–73.

    Article  PubMed  Google Scholar 

  102. Ng D, Toure O, Wei MH, et al. Identification of a novel chromosome region, 13q21.33-q22.2, for susceptibility genes in familial chronic lymphocytic leukemia. Blood. 2007;109:916–25.

    Article  PubMed  CAS  Google Scholar 

  103. Sellick GS, Goldin LR, Wild RW, et al. A high-density SNP genome-wide linkage search of 206 families identifies susceptibility loci for chronic lymphocytic leukemia. Blood. 2007;110:3326–33.

    Article  PubMed  CAS  Google Scholar 

  104. Di Bernardo MC, Crowther-Swanepoel D, Broderick P, et al. A genome-wide association study identifies six susceptibility loci for chronic lymphocytic leukemia. Nat Genet. 2008;40:1204–10.

    Article  PubMed  CAS  Google Scholar 

  105. Slager SL, Kay NE, Fredericksen ZS, et al. Susceptibility genes and B-chronic lymphocytic leukaemia. Br J Haematol. 2007;139:762–71.

    Article  PubMed  Google Scholar 

  106. Crowther-Swanepoel D, Broderick P, Di Bernardo MC, et al. Common variants at 2q37.3, 8q24.21, 15q21.3 and 16q24.1 influence chronic lymphocytic leukemia risk. Nat Genet. 2010;42:132–6.

    Article  PubMed  CAS  Google Scholar 

  107. Crowther-Swanepoel D, Mansouri M, Enjuanes A, et al. Verification that common variation at 2q37.1, 6p25.3, 11q24.1, 15q23, and 19q13.32 influences chronic lymphocytic leukaemia risk. Br J Haematol. 2010;150(4):473–9.

    PubMed  Google Scholar 

  108. Allan JM, Sunter NJ, Bailey JR, et al. Variant IRF4/MUM1 associates with CD38 status and treatment-free survival in chronic lymphocytic leukaemia. Leukemia. 2010;24:877–81.

    Article  PubMed  CAS  Google Scholar 

  109. Juliusson G, Oscier DG, Fitchett M, et al. Prognostic subgroups in B-cell chronic lymphocytic leukemia defined by specific chromosomal abnormalities. N Engl J Med. 1990;323:720–4.

    Article  PubMed  CAS  Google Scholar 

  110. Krober A, Seiler T, Benner A, et al. V(H) mutation status, CD38 expression level, genomic aberrations, and survival in chronic lymphocytic leukemia. Blood. 2002;100:1410–6.

    PubMed  CAS  Google Scholar 

  111. Fitchett M, Griffiths MJ, Oscier DG, Johnson S, Seabright M. Chromosome abnormalities involving band 13q14 in hematologic malignancies. Cancer Genet Cytogenet. 1987;24:143–50.

    Article  PubMed  CAS  Google Scholar 

  112. Zech L, Mellstedt H. Chromosome 13–a new marker for B-cell chronic lymphocytic leukemia. Hereditas. 1988;108:77–84.

    Article  PubMed  CAS  Google Scholar 

  113. Gunnarsson R, Isaksson A, Mansouri M, et al. Large but not small copy-number alterations correlate to high-risk genomic aberrations and survival in chronic lymphocytic leukemia: a high-resolution genomic screening of newly diagnosed patients. Leukemia. 2010;24:211–5.

    Article  PubMed  CAS  Google Scholar 

  114. Haferlach C, Dicker F, Schnittger S, Kern W, Haferlach T. Comprehensive genetic characterization of CLL: a study on 506 cases analysed with chromosome banding analysis, interphase FISH, IgV(H) status and immunophenotyping. Leukemia. 2007;21:2442–51.

    Article  PubMed  CAS  Google Scholar 

  115. Lehmann S, Ogawa S, Raynaud SD, et al. Molecular allelokaryotyping of early-stage, untreated chronic lymphocytic leukemia. Cancer. 2008;112:1296–305.

    Article  PubMed  CAS  Google Scholar 

  116. Pfeifer D, Pantic M, Skatulla I, et al. Genome-wide analysis of DNA copy number changes and LOH in CLL using high-density SNP arrays. Blood. 2007;109:1202–10.

    Article  PubMed  CAS  Google Scholar 

  117. Calin GA, Cimmino A, Fabbri M, et al. MiR-15a and miR-16-1 cluster functions in human leukemia. Proc Natl Acad Sci U S A. 2008;105:5166–71.

    Article  PubMed  CAS  Google Scholar 

  118. Rotman G, Shiloh Y. ATM: from gene to function. Hum Mol Genet. 1998;7:1555–63.

    Article  PubMed  CAS  Google Scholar 

  119. Austen B, Powell JE, Alvi A, et al. Mutations in the ATM gene lead to impaired overall and treatment-free survival that is independent of IGVH mutation status in patients with B-CLL. Blood. 2005;106:3175–82.

    Article  PubMed  CAS  Google Scholar 

  120. Austen B, Skowronska A, Baker C, et al. Mutation status of the residual ATM allele is an important determinant of the cellular response to chemotherapy and survival in patients with chronic lymphocytic leukemia containing an 11q deletion. J Clin Oncol. 2007;25:5448–57.

    Article  PubMed  CAS  Google Scholar 

  121. Bullrich F, Rasio D, Kitada S, et al. ATM mutations in B-cell chronic lymphocytic leukemia. Cancer Res. 1999;59:24–7.

    PubMed  CAS  Google Scholar 

  122. Skinnider BF, Elia AJ, Gascoyne RD, et al. Signal transducer and activator of transcription 6 is frequently activated in Hodgkin and Reed-Sternberg cells of Hodgkin lymphoma. Blood. 2002;99:618–26.

    Article  PubMed  CAS  Google Scholar 

  123. Stankovic T, Weber P, Stewart G, et al. Inactivation of ataxia telangiectasia mutated gene in B-cell chronic lymphocytic leukaemia. Lancet. 1999;353:26–9.

    Article  PubMed  CAS  Google Scholar 

  124. Zenz T, Krober A, Scherer K, et al. Monoallelic TP53 inactivation is associated with poor prognosis in chronic lymphocytic leukemia: results from a detailed genetic characterization with long-term follow-up. Blood. 2008;112:3322–9.

    Article  PubMed  CAS  Google Scholar 

  125. Dicker F, Herholz H, Schnittger S, et al. The detection of TP53 mutations in chronic lymphocytic leukemia independently predicts rapid disease progression and is highly correlated with a complex aberrant karyotype. Leukemia. 2009;23:117–24.

    Article  PubMed  CAS  Google Scholar 

  126. Malcikova J, Smardova J, Rocnova L, et al. Monoallelic and biallelic inactivation of TP53 gene in chronic lymphocytic leukemia: selection, impact on survival, and response to DNA damage. Blood. 2009;114:5307–14.

    Article  PubMed  CAS  Google Scholar 

  127. Rossi D, Spina V, Cerri M, et al. Stereotyped B-cell receptor is an independent risk factor of chronic lymphocytic leukemia transformation to Richter syndrome. Clin Cancer Res. 2009;15: 4415–22.

    Article  PubMed  CAS  Google Scholar 

  128. Tsimberidou AM, Keating MJ. Richter’s transformation in chronic lymphocytic leukemia. Semin Oncol. 2006;33:250–6.

    Article  PubMed  Google Scholar 

  129. Kujawski L, Ouillette P, Erba H, et al. Genomic complexity identifies patients with aggressive chronic lymphocytic leukemia. Blood. 2008;112:1993–2003.

    Article  PubMed  CAS  Google Scholar 

  130. Bjorkholm M, Holm G, De Faire U, Mellsted H. Immunological defects in healthy twin siblings to patients with Hodgkin’s disease. Scand J Haematol. 1977;19:396–404.

    Article  PubMed  CAS  Google Scholar 

  131. Grufferman S, Cole P, Smith PG, Lukes RJ. Hodgkin’s disease in siblings. N Engl J Med. 1977;296:248–50.

    Article  PubMed  CAS  Google Scholar 

  132. Bernard SM, Cartwright RA, Darwin CM, et al. Hodgkin’s disease: case control epidemiological study in Yorkshire. Br J Cancer. 1987;55:85–90.

    Article  PubMed  CAS  Google Scholar 

  133. Goldgar DE, Easton DF, Cannon-Albright LA, Skolnick MH. Systematic population-based assessment of cancer risk in first-degree relatives of cancer probands. J Natl Cancer Inst. 1994;86:1600–8.

    Article  PubMed  CAS  Google Scholar 

  134. Shugart YY, Hemminki K, Vaittinen P, Kingman A, Dong C. A genetic study of Hodgkin’s lymphoma: an estimate of heritability and anticipation based on the familial cancer database in Sweden. Hum Genet. 2000;106:553–6.

    Article  PubMed  CAS  Google Scholar 

  135. Salipante SJ, Mealiffe ME, Wechsler J, et al. Mutations in a gene encoding a midbody kelch protein in familial and sporadic classical Hodgkin lymphoma lead to binucleated cells. Proc Natl Acad Sci U S A. 2009;106:14920–5.

    Article  PubMed  CAS  Google Scholar 

  136. Goldin LR, McMaster ML, Ter-Minassian M, et al. A genome screen of families at high risk for Hodgkin lymphoma: evidence for a susceptibility gene on chromosome 4. J Med Genet. 2005;42:595–601.

    Article  PubMed  CAS  Google Scholar 

  137. Tilly H, Bastard C, Delastre T, et al. Cytogenetic studies in untreated Hodgkin’s disease. Blood. 1991;77:1298–304.

    PubMed  CAS  Google Scholar 

  138. Schouten HC, Sanger WG, Duggan M, Weisenburger DD, MacLennan KA, Armitage JO. Chromosomal abnormalities in Hodgkin’s disease. Blood. 1989;73:2149–54.

    PubMed  CAS  Google Scholar 

  139. Renne C, Martin-Subero JI, Hansmann ML, Siebert R. Molecular cytogenetic analyses of immunoglobulin loci in nodular lymphocyte predominant Hodgkin’s lymphoma reveal a recurrent IGH-BCL6 juxtaposition. J Mol Diagn. 2005;7:352–6.

    Article  PubMed  CAS  Google Scholar 

  140. Martin-Subero JI, Klapper W, Sotnikova A, et al. Chromosomal breakpoints affecting immunoglobulin loci are recurrent in Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma. Cancer Res. 2006;66:10332–8.

    Article  PubMed  CAS  Google Scholar 

  141. Giefing M, Arnemann J, Martin-Subero JI, et al. Identification of candidate tumour suppressor gene loci for Hodgkin and Reed-Sternberg cells by characterisation of homozygous deletions in classical Hodgkin lymphoma cell lines. Br J Haematol. 2008;142: 916–24.

    Article  PubMed  CAS  Google Scholar 

  142. Dohner H, Bloomfield CD, Frizzera G, Frestedt J, Arthur DC. Recurring chromosome abnormalities in Hodgkin’s disease. Genes Chromosomes Cancer. 1992;5:392–8.

    Article  PubMed  CAS  Google Scholar 

  143. Falzetti D, Crescenzi B, Matteuci C, et al. Genomic instability and recurrent breakpoints are main cytogenetic findings in Hodgkin’s disease. Haematologica. 1999;84:298–305.

    PubMed  CAS  Google Scholar 

  144. Hartmann S, Martin-Subero JI, Gesk S, et al. Detection of genomic imbalances in microdissected Hodgkin and Reed-Sternberg cells of classical Hodgkin’s lymphoma by array-based comparative genomic hybridization. Haematologica. 2008;93:1318–26.

    Article  PubMed  CAS  Google Scholar 

  145. Bargou RC, Leng C, Krappmann D, et al. High-level nuclear NF-kappa B and Oct-2 is a common feature of cultured Hodgkin/Reed-Sternberg cells. Blood. 1996;87:4340–7.

    PubMed  CAS  Google Scholar 

  146. Thomas RK, Re D, Wolf J, Diehl V. Part I: Hodgkin’s lymphoma-molecular biology of Hodgkin and Reed-Sternberg cells. Lancet Oncol. 2004;5:11–8.

    Article  PubMed  CAS  Google Scholar 

  147. Barth TF, Martin-Subero JI, Joos S, et al. Gains of 2p involving the REL locus correlate with nuclear c-Rel protein accumulation in neoplastic cells of classical Hodgkin lymphoma. Blood. 2003;101:3681–6.

    Article  PubMed  CAS  Google Scholar 

  148. Jundt F, Anagnostopoulos I, Forster R, Mathas S, Stein H, Dorken B. Activated Notch1 signaling promotes tumor cell pro­liferation and survival in Hodgkin and anaplastic large cell ­lymphoma. Blood. 2002;99:3398–403.

    Article  PubMed  CAS  Google Scholar 

  149. Kube D, Holtick U, Vockerodt M, et al. STAT3 is constitutively activated in Hodgkin cell lines. Blood. 2001;98:762–70.

    Article  PubMed  CAS  Google Scholar 

  150. Schmitz R, Hansmann ML, Bohle V, et al. TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma. J Exp Med. 2009;206:981–9.

    Article  PubMed  CAS  Google Scholar 

  151. Sanchez-Espiridion B, Montalban C, Lopez A, et al. A molecular risk score based on 4 functional pathways for advanced classical Hodgkin lymphoma. Blood. 2010;116:e12–7.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Karolinska University Hospital Solna, Stockholm, 17176, Sweden

    Sigurdur Y. Kristinsson M.D., Ph.D. & Magnus Björkholm M.D., Ph.D.

  2. Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, 75185, Sweden

    Richard Rosenquist M.D., Ph.D.

  3. Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    Ola Landgren M.D., Ph.D.

  4. Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, 20852, USA

    Lynn R. Goldin Ph.D.

Authors
  1. Sigurdur Y. Kristinsson M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richard Rosenquist M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ola Landgren M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lynn R. Goldin Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Magnus Björkholm M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sigurdur Y. Kristinsson M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. Beth Israel Hospital, Cancer Center, St. Lukes-Roosevelt Hospital Center, 10th Avenue 1000, New York, 10019, New York, USA

    Peter H. Wiernik

  2. , Department of Hematology, Imperial College of London, Du Cane Road 150, London, W12 0NN, United Kingdom

    John M. Goldman

  3. Continuum Cancer Centers, Department of Medicine, St. Luke's-Roosevelt Hospital Center, 10th Avenue 1000, New York, 10019, New York, USA

    Janice P. Dutcher

  4. , Division of Hematology, Mayo Clinic, First Street SW. 200, Rochester, 55905, Minnesota, USA

    Robert A. Kyle

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Kristinsson, S.Y., Rosenquist, R., Landgren, O., Goldin, L.R., Björkholm, M. (2013). Genetics in Lymphomagenesis. In: Wiernik, P., Goldman, J., Dutcher, J., Kyle, R. (eds) Neoplastic Diseases of the Blood. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3764-2_40

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-3764-2_40

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-3763-5

  • Online ISBN: 978-1-4614-3764-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation