Current Treatment Options in Oncology

, Volume 7, Issue 4, pp 261–269 | Cite as

Gene expression signatures and outcome prediction in mature B-cell malignancies

  • Sandeep S. Dave

Opinion statement

Non-Hodgkin's lymphomas comprise a diverse group of diseases that are subclassified by the state of differentiation of the malignant B cells, presence of specific cytogenetic abnormalities, and characteristic morphology. Gene expression profiling has revealed that within each category of non-Hodgkin's lymphoma, there exists a significant molecular heterogeneity that can be reflected in differences in tumor behavior and patient outcome. Appreciation of gene expression signatures that are associated with patient outcome will allow better prognostication of disease course and aid the application of molecularly selective patients to improve patient outcome.


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References and Recommended Reading

  1. 1.
    Schena M, Shalon D, Davis RW, Brown PO: Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 1995, 270:467–470.PubMedCrossRefGoogle Scholar
  2. 2.
    Shaffer AL, Rosenwald A, Hurt EM, et al.: Signatures of the immune response. Immunity 2001, 15:375–385. Excellent review of the concept of gene expression signatures and illustration of gene expression signatures that are important in lymphoid malignancies.PubMedCrossRefGoogle Scholar
  3. 3.
    Monti S, Savage KJ, Kutok JL, et al.: Molecular profiling of diffuse large B-cell lymphoma identifies robust subtypes including one characterized by host inflammatory response. Blood 2005, 105:1851–1861.PubMedCrossRefGoogle Scholar
  4. 4.
    Kobayashi T, Kim S, Zhang W, et al.: Gene expression profiling of de novo CD5-positive diffuse large B-cell lymphoma. Rinsho Ketsueki 2003, 44:144–148.PubMedGoogle Scholar
  5. 5.
    Alizadeh AA, Eisen MB, Davis RE, et al.: Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 2000, 403:503–511.PubMedCrossRefGoogle Scholar
  6. 6.
    Wright G, Tan B, Rosenwald A, et al.: A gene expressionbased method to diagnose clinically distinct subgroups of diffuse large B cell lymphoma. Proc Natl Acad Sci U S A 2003, 100:9991–9996.PubMedCrossRefGoogle Scholar
  7. 7.
    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, 346:1937–1947. Comprehensive description of gene expression signatures that distinguish prognostic subgroups within DLBCL.PubMedCrossRefGoogle Scholar
  8. 8.
    Shipp M: A predictive model for aggressive non-Hodgkin's lymphoma. N Engl J Med 1993, 329:987–994.CrossRefGoogle Scholar
  9. 9.
    Lossos IS, Czerwinski DK, Alizadeh AA, et al.: Prediction of survival in diffuse large-B-cell lymphoma based on the expression of six genes. N Engl J Med 2004, 350:1828–1837. Independent validation of findings from the study by Rosenwald et al. [7] and identification of a smaller gene set that can be used to predict prognosis in DLBCL.PubMedCrossRefGoogle Scholar
  10. 10.
    Shipp MA, Ross KN, Tamayo P, et al.: Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and supervised machine learning. Nat Med 2002, 8:68–74.PubMedCrossRefGoogle Scholar
  11. 11.
    Basso K, Margolin AA, Stolovitzky G, et al.: Reverse engineering of regulatory networks in human B cells. Nat Genet 2005, 37:382–390.PubMedCrossRefGoogle Scholar
  12. 12.
    Rimsza LM, Roberts RA, Campo E, et al.: Loss of major histocompatibility class II expression in non-immune privileged site diffuse large B cell lymphoma is highly coordinated and not due to chromosomal deletions. Blood 2005, 107:1101–1107.PubMedCrossRefGoogle Scholar
  13. 13.
    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, 101:4279–4284.PubMedCrossRefGoogle Scholar
  14. 14.
    Winter JN, Weller EA, Horning SJ, et al.: Prognostic significance of Bcl-6 protein expression in DLBCL treated with CHOP or R-CHOP: a prospective correlative study. Blood 2006, In press.Google Scholar
  15. 15.
    Horning SJ: Follicular lymphoma: have we made any progress. Ann Oncol 2000, 11(Suppl 1):23–27.PubMedCrossRefGoogle Scholar
  16. 16.
    Shaffer AL, Rosenwald A, Staudt LM: Lymphoid malignancies: the dark side of B-cell differentiation. Nat Rev Immunol 2002, 2:920–932.PubMedCrossRefGoogle Scholar
  17. 17.
    Lossos IS, Levy R: Higher grade transformation of follicular lymphoma: phenotypic tumor progression associated with diverse genetic lesions. Semin Cancer Biol 2003, 13:191–202.PubMedCrossRefGoogle Scholar
  18. 18.
    Dave SS, Wright G, Tan B, et al.: Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. N Engl J Med 2004, 351:2159–2169. Demonstration of effects of nonmalignant cells in predicting long-term survival in patients with follicular lymphoma.PubMedCrossRefGoogle Scholar
  19. 19.
    Farinha P, Masoudi H, Skinnider BF, et al.: Analysis of multiple biomarkers shows that lymphoma-associated macrophage (LAM) content is an independent predictor of survival in follicular lymphoma (FL). Blood 2005, 106:2169–2174.PubMedCrossRefGoogle Scholar
  20. 20.
    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, 3:185–197. Demonstration of the proliferation gene expression signature and its association with survival as well as several independent oncogenic events.PubMedCrossRefGoogle Scholar
  21. 21.
    Velders GA, Kluin-Nelemans JC, De Boer CJ, et al.: Mantle-cell lymphoma: a population-based clinical study. J Clin Oncol 1996, 14:1269–1274.PubMedGoogle Scholar
  22. 22.
    Addis BJ, Isaacson PG: Large cell lymphoma of the mediastinum: a B-cell tumour of probable thymic origin. Histopathology 1986, 10:379–390.PubMedCrossRefGoogle Scholar
  23. 23.
    Savage KJ, Monti S, Kutok JL, 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, 102:3871–3879. Demonstration of a distinct subgroup of DLBCL with a distinctive gene expression profile.PubMedCrossRefGoogle Scholar
  24. 24.
    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 Exp Med 2003, 198:851–862. Demonstration of a distinct subgroup of DLBCL with a distinctive gene expression profile.PubMedCrossRefGoogle Scholar
  25. 25.
    Rosenwald A, Alizadeh AA, Widhopf G, et al.: Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia. J Exp Med 2001, 194:1639–1648.PubMedCrossRefGoogle Scholar
  26. 26.
    Wiestner A, Rosenwald A, Barry TS, et al.: ZAP-70 expression identifies a chronic lymphocytic leukemia subtype with unmutated immunoglobulin genes, inferior clinical outcome, and distinct gene expression profile. Blood 2003, 101:4944–4951.PubMedCrossRefGoogle Scholar
  27. 27.
    Crespo M, Bosch F, Villamor N, et al.: ZAP-70 expression as a surrogate for immunoglobulin-variableregion mutations in chronic lymphocytic leukemia. N Engl J Med 2003, 348:1764–1775.PubMedCrossRefGoogle Scholar
  28. 28.
    Rassenti LZ, Huynh L, Toy TL, et al.: ZAP-70 compared with immunoglobulin heavy-chain gene mutation status as a predictor of disease progression in chronic lymphocytic leukemia. N Engl J Med 2004, 351:893–901.PubMedCrossRefGoogle Scholar
  29. 29.
    Hoefnagel JJ, Dijkman R, Basso K, et al.: Distinct types of primary cutaneous large B-cell lymphoma identified by gene expression profiling. Blood 2005, 105:3671–3678.PubMedCrossRefGoogle Scholar
  30. 30.
    Ruiz-Ballesteros E, Mollejo M, Rodriguez A, et al.: Splenic marginal zone lymphoma: proposal of new diagnostic and prognostic markers identified after tissue and cDNA microarray analysis. Blood 2005, 106:1831–1838.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc 2006

Authors and Affiliations

  • Sandeep S. Dave
    • 1
  1. 1.National Cancer InstituteBethesdaUSA

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