ABSTRACT
Historic perspective 1463 Molecular profiling: technical and analytical considerations 1464 Current status of gene expression profiling in lymphoma 1464
diagnosis Gene expression profiling and prediction of outcome 1468 Epigenetic modulation in lymphomas 1469
Profiles of aberrant promoter CpG methylation in human 1470 lymphoid neoplasia
Future directions 1472 Targeting epigenetic pathways: therapeutic approaches 1474 Key points 1475 References 1476
In the past two decades, there have been major advances in our understanding of the pathogenesis and biology of lymphoid malignancies.1,2 Translocation breakpoints associated with many types of lymphomas3-5 have been cloned and their mechanisms of action are being elucidated. Many genetic abnormalities or markers with significant diagnostic or prognostic importance have also been identified. One excellent example is the translocations involving the MALT1 gene in extranodal marginal zone lymphoma (EMZL).6,7 In gastric EMZL, the presence of this translocation indicates that the tumor is no longer responsive to antibiotic therapy directed against Helicobacter pylori.8 In addition, these tumors have a spectrum of genetic abnormalities different from ones present in tumors without the translocation and, interestingly, they rarely progress to a diffuse large B cell lymphoma (DLBCL).9 Inactivation of tumor suppressor genes such as TP53, p16INK4a, and p27 and abnormalities in the apoptotic pathways have been associated with poorer survival or tumor progression in a number of lymphomas.10-16 Molecular diagnostics should not only serve as an aid to render a diagnosis, but also should measure parameters that are relevant to the biologic and clinical behavior of a tumor.
