Biology of the lymphomas: cytogenetics, molecular biology, and virology.
Correlations between cytogenetics, histology, and clinical course continue to emerge in studies of non-Hodgkin's lymphomas. The previously recognized association between the t(14;18) chromosomal translocation and follicular lymphoma has been confirmed; abnormalities of chromosome 3 have correlated specifically with diffuse large cell lymphoma and abnormalities of chromosome 1 have been frequently present in T-cell lymphomas. Rearrangements involving 11q13 (bcl-1) occur most commonly in diffuse lymphocytic lymphoma of intermediate differentiation. Several new recurrent chromosomal abnormalities have also been described. The molecular fine structure of the t(8-14) chromosomal translocation in Burkitt's lymphoma appears to differ between endemic (Epstein-Barr virus-associated) and sporadic cases. In endemic Burkitt's lymphomas, the chromosomal breakpoint is usually far upstream of c-myc oncogene, leaving the regulatory region of the gene intact. In sporadic tumors, a large part of the regulatory region is separated from the gene and transcription is initiated at sites within the first intron. These data raise the possibility that Epstein-Barr virus may contribute to the deregulation of the c-myc gene and that this interaction may be required for tumorigenesis in the presence of some, but not all, types of c-myc damage arising from chromosomal translocations. Partner proteins that oligomerize with c-Myc have been identified in humans and mice (Max and Myn). The partners share with c-Myc the DNA-binding and coiled-coil motifs that are recognized in many other proteins and that function as transcriptional regulators. The Bcl-2 protein has been shown to be a mitochondrial inner membrane protein that blocks programmed cell death (apoptosis). Viral expression has been demonstrated in Epstein-Barr virus-associated Hodgkin's disease, and the spectrum of Epstein-Barr virus-associated lymphoproliferative disease has been expanded to include some T-cell malignancies. A new human herpesvirus has been associated with some cases of Hodgkin's disease.
Ambinder
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Johns Hopkins Oncology Center, Baltimore, Maryland.
Griffin
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CA
D000818:Animals; D002051:Burkitt Lymphoma / Q000235:genetics / Q000382:microbiology; D016923:Cell Death; D002880:Chromosomes, Human, Pair 11 / Q000648:ultrastructure; D002883:Chromosomes, Human, Pair 14 / Q000648:ultrastructure; D002887:Chromosomes, Human, Pair 18 / Q000648:ultrastructure; D002898:Chromosomes, Human, Pair 8 / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000502:physiology; D015967:Gene Expression Regulation, Viral; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D016259:Genes, myc; D004854:Herpesvirus 4, Human / Q000472:pathogenicity; D006801:Humans; D016350:Leucine Zippers; D008223:Lymphoma / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000502:physiology; D011519:Proto-Oncogenes; D014178:Translocation, Genetic; D014412:Tumor Virus Infections / Q000235:genetics
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc