Distinguishing between monoclonal rearrangements and allelic forms of the immunoglobulin lambda light chain constant region genes. Significance in the diagnosis of non-Hodgkin's lymphoma.
Four allelic forms of the immunoglobulin lambda light chain constant region (C lambda) genes are found in the caucasoid population and are recognised by the presence of Eco RI restriction fragments of sizes 8, 13, 18, and 23 kb hybridising with a C lambda probe. The less common allelic forms of the C lambda genes are marked by the 13, 18, and 23 kb fragments, and these may be misinterpreted as rearranged fragments derived from a monoclonal population of B-cells. The 13, 18, and 23 kb alleles result from the insertion of one, two, and three copies, respectively, of a 5.2 kb repeat unit that can be demonstrated by hybridising genomic DNA digested with Hind III with a C lambda probe. Using selected histologically and immunophenotypically well-defined cases, we assessed the usefulness of the 5.2 kb Hind III/C lambda fragment in distinguishing between rearrangements indicative of a B-cell lymphoma and germline configurations representing uncommon allelic forms of the C lambda genes. From these studies, we conclude that Hind III digestion should routinely be performed when using the C lambda probe to assess B-cell monoclonality. Identification of the 5.2 kb Hind III fragment obviates the need to examine DNA from normal peripheral blood granulocytes to exclude allelism of the C lambda genes in cases exhibiting the uncommon restriction fragments after Eco RI digestion.
Saueracker
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Department of Pathology, Sir Charles Gairdner Hospital, Nedlands, Western Australia.
Kay
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Spagnolo
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D000328:Adult; D000368:Aged; D000483:Alleles; D002648:Child; D005260:Female; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D005803:Genes, Immunoglobulin; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007146:Immunoglobulin lambda-Chains / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length
D007127:Immunoglobulin Constant Regions; D007146:Immunoglobulin lambda-Chains