Gene Expression Profiling of Non-Hodgkin Lymphomas

  • Zekri, Abdel-Rahman Nabawy (Virology and Immunology Unit, Cancer Biology Department, Faculty of Medicine National Cancer Institute, Cairo University) ;
  • Hassan, Zeinab Korany (Virology and Immunology Unit, Cancer Biology Department, Faculty of Medicine National Cancer Institute, Cairo University) ;
  • Bahnassy, Abeer Ahmed (Clinical Pathology Department, Faculty of Medicine National Cancer Institute, Cairo University) ;
  • Eldahshan, Dina Hassan (Clinical Pathology Department, Faculty of Medicine National Cancer Institute, Cairo University) ;
  • El-Rouby, Mahmoud Nour Eldin (Virology and Immunology Unit, Cancer Biology Department, Faculty of Medicine National Cancer Institute, Cairo University) ;
  • Kamel, Mahmoud Mohamed (Clinical Pathology Department, Faculty of Medicine National Cancer Institute, Cairo University) ;
  • Hafez, Mohamed Mahmoud (Virology and Immunology Unit, Cancer Biology Department, Faculty of Medicine National Cancer Institute, Cairo University)
  • Published : 2013.07.30


Background: Chromosomal translocations are genetic aberrations associated with specific non-Hodgkin lymphoma (NHL) subtypes. This study investigated the differential gene expression profile of Egyptian NHL cases based on a microarray approach. Materials and Methods: The study included tissue samples from 40 NHL patients and 20 normal lymph nodes used as controls. Total RNA was extracted and used for cDNA microarray assays. The quantitative real time polymerase chain reaction was used to identify the aberrantly expressed genes in cancer. Results: Significant associations of 8 up-regulated and 4 down-regulated genes with NHL were observed. Aberrant expression of a new group of genes not reported previously was apparent, including down-regulated NAG14 protein, 3 beta hydroxy-delta 5-c27 steroid oxi-reductase, oxi-glutarate dehydrogenase (lipo-amide), immunoglobulin lambda like polypeptide 3, protein kinase x linked, Hmt1, and caveolin 2 Tetra protein. The up-regulated genes were Rb binding protein 5, DKFZP586J1624 protein, protein kinase inhibitor gamma, zinc finger protein 3, choline ethanolamine phospho-transferase CEPT1, protein phosphatase, and histone deacetylase-3. Conclusions: This study revealed that new differentially expressed genes that may be markers for NHL patients and individuals who are at high risk for cancer development.


Non-hodgkin lymphoma;cDNA microarray;up-regulation;down-regulation;markers


  1. Adhikary S, Eilers M (2005). Transcriptional regulation and transformation by Myc proteins. Nat Rev Mol Cell Biol, 6, 635-45.
  2. Alizadeh AA, Eisen MB, Davis RE, et al (2000). Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature, 403, 503-11.
  3. Allan LA, Clarke PR (2009). Apoptosis and autophagy: Regulation of caspase-9 by phosphorylation. FEBS J, 276, 6063-73.
  4. Alpen B, Robbecke J, Wundisch T, Stolte M, Neubauer A (2001). Helicobacter pylori eradication therapy in gastric high grade non Hodgkin's lymphoma (NHL). Ann Hematol, 80, 106-7.
  5. Baraniskin A, Deckert M, Schulte-Altedorneburg G, Schlegel U, Schroers R (2012). Current strategies in the diagnosis of diffuse large B-cell lymphoma of the central nervous system. Br J Haematol, 156, 421-32.
  6. Bea S, Zettl A, Wright G, et al (2005). Diffuse large B-cell lymphoma subgroups have distinct genetic profiles that influence tumor biology and improve gene-expression-based survival prediction. Blood, 106, 3183-90.
  7. Bende RJ, Smit LA, van Noesel CJ (2007). Molecular pathways in follicular lymphoma. Leukemia, 21, 18-29.
  8. Berget E, Helgeland L, Lehmann AK, et al (2012). Primary diffuse large B-cell lymphoma of the dura without systemic recurrence four years after diagnosis and successful therapy. Acta Oncol, 52, 1047-9.
  9. Biasoli I, Morais JC, Scheliga A, et al (2005). CD10 and Bcl- 2 expression combined with the International Prognostic Index can identify subgroups of patients with diffuse largecell lymphoma with very good or very poor prognoses. Histopathology, 46, 328-33.
  10. Bouillet P, Metcalf D, Huang DC, et al (1999). Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity. Science, 286, 1735-8.
  11. Charbonneau B, Maurer MJ, Fredericksen ZS, et al (2012). Germline variation in complement genes and event-free survival in follicular and diffuse large B-cell lymphoma. Am J Hematol, 87, 880-5.
  12. Dyer MJ (2003). The pathogenetic role of oncogenes deregulated by chromosomal translocation in B-cell malignancies. Int J Hematol, 77, 315-20.
  13. Gouda I, Nada O, Ezzat S, et al (2010). Immunohistochemical detection of hepatitis C virus (genotype 4) in B-cell NHL in an Egyptian population: correlation with serum HCV-RNA. Appl Immunohistochem Mol Morphol, 18, 29-34.
  14. Guo YL, Dong LL, Gao L, et al (2012). Clinical significance of rapid detecting bone marrow BCL2/IGH and BCL6/IGH fusion genes in patients with diffuse large B cell lymphoma by multiplex PCR. Zhongguo Shi Yan Xue Ye Xue Za Zhi, 20, 1370-3.
  15. Harada H, Quearry B, Ruiz-Vela A, Korsmeyer SJ (2004). Survival factor-induced extracellular signal-regulated kinase phosphorylates BIM, inhibiting its association with BAX and proapoptotic activity. Proc Natl Acad Sci USA, 101, 15313-7.
  16. Ibrahim A, Abdel Rahman H, Khorshied M, et al (2012). Tumor necrosis factor alpha-308 and Lymphotoxin alpha+252 genetic polymorphisms and the susceptibility to non- Hodgkin lymphoma in Egypt. Leuk Res, 36, 694-8.
  17. Iqbal J, Greiner TC, Patel K, et al (2007). Distinctive patterns of BCL6 molecular alterations and their functional consequences in different subgroups of diffuse large B-cell lymphoma. Leukemia, 21, 2332-43.
  18. Jardin F, Ruminy P, Bastard C, Tilly H (2007). The BCL6 protooncogene: a leading role during germinal center development and lymphomagenesis. Pathol Biol, 55, 73-83.
  19. Jardin F, Ruminy P, Parmentier F, et al (2005). Clinical and biological relevance of single-nucleotide polymorphisms and acquired somatic mutations of the BCL6 first intron in follicular lymphoma. Leukemia, 19, 1824-30.
  20. Kanavaros P, De Bruin PC, Briere J, Meijer CJ, Gaulard P (1995). Epstein-Barr virus (EBV) in extranodal T-cell non-Hodgkin's lymphomas (T-NHL). Identification of nasal T-NHL as a distinct clinicopathological entity associated with EBV. Leuk Lymphoma, 18, 27-34.
  21. Khanna KK, Wie T, Song Q, et al (1996). Expression of p53, bcl-2, bax, bcl-x2 and c-myc in radiation-induced apoptosis in Burkitt's lymphoma cells. Cell Death Differ, 3, 315-22.
  22. Killebrew D, Shiramizu B (2004). Pathogenesis of HIVassociated non-Hodgkin lymphoma. Curr HIV Res, 2, 215-21.
  23. Kuppers R (2005). Mechanisms of B-cell lymphoma pathogenesis. Nat Rev Cancer, 5, 251-62.
  24. Kuppers R, Dalla-Favera R (2001). Mechanisms of chromosomal translocations in B cell lymphomas. Oncogene, 20, 5580-94.
  25. Lewin N, Aman P, Mellstedt H, et al (1990). Epstein Barr virus (EBV) carrying cells in blood of Hodgkin's disease (HD) and non-Hodgkin lymphoma (NHL) patients with high antibody titers against EBV capsid antigens (VCA). Anticancer Res, 10, 1213-6.
  26. Lossos IS, Akasaka T, Martinez-Climent JA, Siebert R, Levy R (2003). The BCL6 gene in B-cell lymphomas with 3q27 translocations is expressed mainly from the rearranged allele irrespective of the partner gene. Leukemia, 17, 1390-7.
  27. Lossos IS, Jones CD, Warnke R, et al (2001). Expression of a single gene, BCL-6, strongly predicts survival in patients with diffuse large B-cell lymphoma. Blood, 98, 945-51.
  28. Marcucci F, Mele A (2011). Hepatitis viruses and non-Hodgkin lymphoma: epidemiology, mechanisms of tumorigenesis, and therapeutic opportunities. Blood, 117, 1792-8.
  29. Martinez-Delgado B, Melendez B, Cuadros M, et al (2004). Expression profiling of T-cell lymphomas differentiates peripheral and lymphoblastic lymphomas and defines survival related genes. Clin Cancer Res, 10, 4971-82.
  30. Mey U, Hitz F, Lohri A, et al (2012). Diagnosis and treatment of diffuse large B-cell lymphoma. Swiss Med Wkly, 142, 0.
  31. Morton LM, Purdue MP, Zheng T, et al (2009). Risk of non- Hodgkin lymphoma associated with germline variation in genes that regulate the cell cycle, apoptosis, and lymphocyte development. Cancer Epidemiol Biomarkers Prev, 18, 1259-70.
  32. Muramatsu M, Akasaka T, Kadowaki N, et al (1996). Rearrangement of the BCL6 gene in B-cell lymphoid neoplasms: comparison with lymphomas associated with BCL2 rearrangement. Br J Haematol, 93, 911-20.
  33. Nasr AS, Sami RM, Ibrahim NY (2012). Methylenetetrahydrofolate reductase gene polymorphisms (677C>T and 1298A>C) in Egyptian patients with non-Hodgkin lymphoma. J Cancer Res Ther, 8, 355-60.
  34. Naz E, Mirza T, Danish F (2011). Clinicopathologic evaluation of subgroups of diffuse large B cell lymphoma by immunohistochemistry. Asian Pac J Cancer Prev, 12, 3335-9.
  35. Ohno H (2006). Pathogenetic and clinical implications of non-immunoglobulin; BCL6 translocations in B-cell non- Hodgkin's lymphoma. J Clin Exp Hematop, 46, 43-53.
  36. Pasqualucci L, Compagno M, Houldsworth J, et al (2006). Inactivation of the PRDM1/BLIMP1 gene in diffuse large B cell lymphoma. J Exp Med, 203, 311-7.
  37. Porcu P, Nichols CR (1998). Evaluation and management of the "new" lymphoma entities: mantle cell lymphoma, lymphoma of mucosa-associated lymphoid tissue, anaplastic large-cell lymphoma, and primary mediastinal B-cell lymphoma. Curr Probl Cancer, 22, 283-368.
  38. Reed JC, Miyashita T, Krajewski S, et al (1996). Bcl-2 family proteins and the regulation of programmed cell death in leukemia and lymphoma. Cancer Treat Res, 84, 31-72.
  39. Staudt LM, Dave S (2005). The biology of human lymphoid malignancies revealed by gene expression profiling. Adv Immunol, 87, 163-208.
  40. Tate G, Kishimoto K, Hirayama Y, Suzuki T, Mitsuya T (2009). A novel missense mutation of the XBP1 gene in diffuse large B-cell lymphoma. Cancer Genet Cytogenet, 190, 131-3.
  41. Tilly H, Vitolo U, Walewski J, et al (2012). Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol, 23, 778-82.
  42. van Doorn R, Zoutman WH, Dijkman R, et al (2005). Epigenetic profiling of cutaneous T-cell lymphoma: promoter hypermethylation of multiple tumor suppressor genes including BCL7a, PTPRG, and p73. J Clin Oncol, 23, 3886-96.
  43. Wright G, Tan B, Rosenwald A, et al (2003). A gene expressionbased method to diagnose clinically distinct subgroups of diffuse large B cell lymphoma. Proc Natl Acad Sci USA, 100, 9991-6.
  44. Zani VJ, Asou N, Jadayel D, et al (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, 3124-34.
  45. Zantl N, Weirich G, Zall H, et al (2007). Frequent loss of expression of the pro-apoptotic protein Bim in renal cell carcinoma: evidence for contribution to apoptosis resistance. Oncogene, 26, 7038-48.
  46. Zhang Y, Lan Q, Rothman N, et al (2005). A putative exonic splicing polymorphism in the BCL6 gene and the risk of non-Hodgkin lymphoma. J Natl Cancer Inst, 97, 1616-8.

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