Identification of a common clonal human immunodeficiency virus integration site in human immunodeficiency virus-associated lymphomas.
Infection with human immunodeficiency virus type 1 (HIV-1) is associated with a high incidence of lymphoma. Typically, the lymphomas are B-cell in origin, and although they occur in the setting of HIV-1 infection, historical studies have found no evidence for the presence of HIV-1 within the transformed B-cells. We describe a new class of large cell lymphoma wherein HIV p24 expression within the tumor specimens was found to be extremely high. In the first case, HIV was expressed in the tumor-associated transformed T-cells. In three other cases, HIV was found to be highly expressed in tumor-associated macrophages. These tumors exhibited a mixed immunophenotype histologically. Analysis by inverse polymerase chain reaction, using HIV long terminal repeat primers, demonstrated monoclonal HIV integration sites for all four tumors. Direct sequencing of the T-cell lymphoma inverse polymerase chain reaction products identified the HIV integration site within the fur gene, just upstream from the c-fes/fps protooncogene. Using segments of the fur gene as a probe, the other three monoclonal integration sites mapped to the same region. Although the integration and up-regulation of c-fes/fps was localized to the tumor cells within the T-cell lymphoma, the cells containing the monoclonal HIV in the other mixed immunophenotype lymphomas are currently unknown. These observations suggest that HIV may contribute directly to lymphomagenesis and identify a common site of HIV integration within a subset of acquired immunodeficiency syndrome lymphoma.
Shiramizu
B
B
Department of Pediatrics, San Francisco General Hospital, University of California 94110.
Herndier
B G
BG
McGrath
M S
MS
D001483:Base Sequence; D017931:DNA Primers; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D016130:Immunophenotyping; D016483:Lymphoma, AIDS-Related / Q000235:genetics* / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051578:Proto-Oncogene Proteins c-fes; D011519:Proto-Oncogenes; D015183:Restriction Mapping; D016662:Virus Integration
D017931:DNA Primers; D015345:Oligonucleotide Probes; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C496645:FES protein, human; D051578:Proto-Oncogene Proteins c-fes