Biologic and molecular characterization of non-Hodgkin's lymphoma.
The wide clinicopathologic heterogeneity of non-Hodgkin's lymphoma is reflected by the various molecular pathways underlying non-Hodgkin's lymphoma pathogenesis, including activation of dominantly acting oncogenes, deletion and inactivation of tumor-suppressor genes, viral infection, deregulation of cytokine networks, and chronic antigenic stimulation. Molecular lesions involving protooncogenes include activation of bcl-2 and bcl-1 in specific subsets of low-grade non-Hodgkin's lymphomas and c-myc in a proportion of intermediate- and high-grade non-Hodgkin's lymphomas. The deregulation of these genes promotes cell growth or protects the tumor population from programmed cell death, or both. Additional genetic abnormalities representing putative sites of novel oncogenes contributing to lymphomagenesis include chromosomal breaks at 3q27 in intermediate-grade non-Hodgkin's lymphoma and at 9p13 in small lymphocytic lymphoma. The role of inactivation of tumor-suppressor loci is best exemplified by the frequent inactivation of p53 in Burkitt's lymphoma and by the recurrent deletion of 6q25-q27 and 6q21-q23 in intermediate- and high-grade non-Hodgkin's lymphoma, respectively. Infection by Epstein-Barr virus occurs in a variable fraction of high-grade non-Hodgkin's lymphomas, whereas it is usually absent in other types of non-Hodgkin's lymphoma. Other mechanisms supporting non-Hodgkin's lymphoma growth and development include autocrine or paracrine cytokine loops, or both, and clonal expansion through antigen receptor stimulation. The heterogeneity of non-Hodgkin's lymphoma pathogenesis provides a framework for the development of novel classification methods of potential clinical relevance.
Gaidano
G
G
Columbia University, New York, New York, USA.
Dalla-Favera
R
R
D019938:Cyclin D1; D016207:Cytokines / Q000494:pharmacology; D016147:Genes, Tumor Suppressor; D016259:Genes, myc; D004854:Herpesvirus 4, Human / Q000472:pathogenicity; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000209:etiology / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D014178:Translocation, Genetic
D016207:Cytokines; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019938:Cyclin D1