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Rearrangements of Both Homologues of Chromosome 14 in Lymphoma

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Fiscal Year:
2010
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Product Description:
Chromosomal rearrangements of the immunoglobulin heavy chain (IgH) gene, localized at 14q32, have been associated with both Hodgkin and non-Hodgkin lymphoma (NHL). The most common abnormality results in a translocation where the promoter region for IgH is brought into close proximity of a few select oncogenes, causing them to be upregulated. Most often, only one chromosome 14 homolog is involved, leaving the second IgH gene intact. A few cases have been reported in which an abnormality involving both IgH loci occurs. To date, no studies have focused on the clinical relevance of the involvement of both homologues of 14 in lymphomas. Disruption of both 14q32 (the IgH gene locus) or loss of one 14q32 region and a disruption of the other may lead to complete loss of a normal functional copy of the IgH gene. In a review of histologically confirmed lymphomas characterized by conventional cytogenetics and/or fluorescence in situ hybridization (FISH) at the University of Nebraska Medical Center in the past decade, seven NHL cases were found to contain abnormalities involving both 14q32 loci. Cases with polyploidy or hyperdiploidy with at least one intact copy of 14q32 (IgH) were not considered among these double 14q32 involvements. Since the t(14;18) is the most frequently reported translocation in NHL, it is not surprising that four out of the seven cases observed included this translocation along with either a secondary translocation, characterized as added material of unknown origin at the second 14q32 locus i.e. add (14)(q32), or complete loss of the homologous chromosome. Of the three remaining cases, one had a t(8;14)(q24.1;q32) with a der(14)t(8;14); the second case a t(11;14) with loss of the homologous chromosome; and the third case was characterized by a t(11;14) and a t(8;14) detected by FISH. Although the complete loss of normal IgH gene function is a relatively rare event, it may likely be associated with pathogenesis and progression in NHL. Additional clinical correlations may help determine prognostic impact of this phenomenon.
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Conference presentations and posters presented
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Professionals, Students
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