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. 1985 Apr 1;161(4):850–863. doi: 10.1084/jem.161.4.850

Frequent biclonality and Ig gene alterations among B cell lymphomas that show multiple histologic forms

PMCID: PMC2189062  PMID: 2984307

Abstract

Configurations of Ig gene DNA were examined in multiple biopsy specimens from seven cases of human B cell lymphoma that showed histologic differences among the specimens within each case. Analysis by Southern blot hybridizations with DNA probes for each of the three Ig loci revealed that the configurations of DNA within these loci were identical among the specimens in two of the cases. This result indicated the monoclonality of these lymphomas, despite differences in histology between biopsy specimens. In contrast, no common nongermline configurations of Ig gene DNA were detected among multiple biopsies in each of three other cases. Therefore, different histologies correlated with separate clones of proliferating B cells in these cases. In the last two cases, the configurations of light chain gene DNA were the same among biopsies in each case, consistent with a monoclonal origin in both lymphomas. However, differences were detected in the configuration of the heavy chain gene DNA. Analysis with a series of DNA probes of the mu heavy chain region indicated that the differences in the DNA configurations of the heavy chain genes from the biopsies probably arose from postrearrangement deletions of either the switch or constant regions of the mu gene. These studies indicate that, contrary to the conventional belief, individual tumors that contain different histologic types of lymphoma within the same patient frequently arise from separate clones of neoplastic cells. Furthermore, the heavy chain genes of monoclonal tumors may show postrearrangement deletions, often resulting from instability of DNA sequences within or around the mu switch region.

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Selected References

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  1. Acker B., Hoppe R. T., Colby T. V., Cox R. S., Kaplan H. S., Rosenberg S. A. Histologic conversion in the non-Hodgkin's lymphomas. J Clin Oncol. 1983 Jan;1(1):11–16. doi: 10.1200/JCO.1983.1.1.11. [DOI] [PubMed] [Google Scholar]
  2. Alexander A., Steinmetz M., Barritault D., Frangione B., Franklin E. C., Hood L., Buxbaum J. N. gamma Heavy chain disease in man: cDNA sequence supports partial gene deletion model. Proc Natl Acad Sci U S A. 1982 May;79(10):3260–3264. doi: 10.1073/pnas.79.10.3260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Alt F. W., Yancopoulos G. D., Blackwell T. K., Wood C., Thomas E., Boss M., Coffman R., Rosenberg N., Tonegawa S., Baltimore D. Ordered rearrangement of immunoglobulin heavy chain variable region segments. EMBO J. 1984 Jun;3(6):1209–1219. doi: 10.1002/j.1460-2075.1984.tb01955.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Alt F., Rosenberg N., Lewis S., Thomas E., Baltimore D. Organization and reorganization of immunoglobulin genes in A-MULV-transformed cells: rearrangement of heavy but not light chain genes. Cell. 1981 Dec;27(2 Pt 1):381–390. doi: 10.1016/0092-8674(81)90421-9. [DOI] [PubMed] [Google Scholar]
  5. Cleary M. L., Chao J., Warnke R., Sklar J. Immunoglobulin gene rearrangement as a diagnostic criterion of B-cell lymphoma. Proc Natl Acad Sci U S A. 1984 Jan;81(2):593–597. doi: 10.1073/pnas.81.2.593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cleary M. L., Sklar J. Lymphoproliferative disorders in cardiac transplant recipients are multiclonal lymphomas. Lancet. 1984 Sep 1;2(8401):489–493. doi: 10.1016/s0140-6736(84)92566-2. [DOI] [PubMed] [Google Scholar]
  7. Cleary M. L., Warnke R., Sklar J. Monoclonality of lymphoproliferative lesions in cardiac-transplant recipients. Clonal analysis based on immunoglobulin-gene rearrangements. N Engl J Med. 1984 Feb 23;310(8):477–482. doi: 10.1056/NEJM198402233100801. [DOI] [PubMed] [Google Scholar]
  8. Dick F. R., Parks W., O'Connor M. Transformation of nodular lymphoma to an immunoblastic IgM-producing tumor. Am J Clin Pathol. 1977 Nov;68(5):611–615. doi: 10.1093/ajcp/68.5.611. [DOI] [PubMed] [Google Scholar]
  9. Erikson J., Finan J., Tsujimoto Y., Nowell P. C., Croce C. M. The chromosome 14 breakpoint in neoplastic B cells with the t(11;14) translocation involves the immunoglobulin heavy chain locus. Proc Natl Acad Sci U S A. 1984 Jul;81(13):4144–4148. doi: 10.1073/pnas.81.13.4144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hieter P. A., Hollis G. F., Korsmeyer S. J., Waldmann T. A., Leder P. Clustered arrangement of immunoglobulin lambda constant region genes in man. Nature. 1981 Dec 10;294(5841):536–540. doi: 10.1038/294536a0. [DOI] [PubMed] [Google Scholar]
  11. Hieter P. A., Korsmeyer S. J., Waldmann T. A., Leder P. Human immunoglobulin kappa light-chain genes are deleted or rearranged in lambda-producing B cells. Nature. 1981 Apr 2;290(5805):368–372. doi: 10.1038/290368a0. [DOI] [PubMed] [Google Scholar]
  12. Hubbard S. M., Chabner B. A., DeVita V. T., Jr, Simon R., Berard C. W., Jones R. B., Garvin A. J., Canellos G. P., Osborne C. K., Young R. C. Histologic progression in non-Hodgkin's lymphoma. Blood. 1982 Feb;59(2):258–264. [PubMed] [Google Scholar]
  13. Jaffe E. S., Braylan R. C., Nanba K., Frank M. M., Berard C. W. Functional markers: a new perspective on malignant lymphomas. Cancer Treat Rep. 1977 Sep;61(6):953–962. [PubMed] [Google Scholar]
  14. Levy R., Warnke R., Dorfman R. F., Haimovich J. The monoclonality of human B-cell lymphomas. J Exp Med. 1977 Apr 1;145(4):1014–1028. doi: 10.1084/jem.145.4.1014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mills F. C., Fisher L. M., Kuroda R., Ford A. M., Gould H. J. DNase I hypersensitive sites in the chromatin of human mu immunoglobulin heavy-chain genes. Nature. 1983 Dec 22;306(5945):809–812. doi: 10.1038/306809a0. [DOI] [PubMed] [Google Scholar]
  16. Mushinski J. F. Gamma-A half molecules: defective heavy chain mutants in mouse myeloma proteins. J Immunol. 1971 Jan;106(1):41–50. [PubMed] [Google Scholar]
  17. Nowell P., Finan J., Glover D., Guerry D. Cytogenetic evidence for the clonal nature of Richter's syndrome. Blood. 1981 Jul;58(1):183–186. [PubMed] [Google Scholar]
  18. POTTER M., KUFF E. L. DISORDERS IN THE DIFFERENTIATON OF PROTEIN SECRETION IN NEOPLASTIC PLASMA CELLS. J Mol Biol. 1964 Aug;9:537–544. doi: 10.1016/s0022-2836(64)80225-4. [DOI] [PubMed] [Google Scholar]
  19. Pettersson U., Sambrook J. Amount of viral DNA in the genome of cells transformed by adenovirus type 2. J Mol Biol. 1973 Jan;73(1):125–130. doi: 10.1016/0022-2836(73)90164-2. [DOI] [PubMed] [Google Scholar]
  20. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  21. Sklar J., Cleary M. L., Thielemans K., Gralow J., Warnke R., Levy R. Biclonal B-cell lymphoma. N Engl J Med. 1984 Jul 5;311(1):20–27. doi: 10.1056/NEJM198407053110104. [DOI] [PubMed] [Google Scholar]
  22. Taub R. A., Hollis G. F., Hieter P. A., Korsmeyer S., Waldmann T. A., Leder P. Variable amplification of immunoglobulin lambda light-chain genes in human populations. Nature. 1983 Jul 14;304(5922):172–174. doi: 10.1038/304172a0. [DOI] [PubMed] [Google Scholar]
  23. Teillaud J. L., Desaymard C., Giusti A. M., Haseltine B., Pollock R. R., Yelton D. E., Zack D. J., Scharff M. D. Monoclonal antibodies reveal the structural basis of antibody diversity. Science. 1983 Nov 18;222(4625):721–726. doi: 10.1126/science.6356353. [DOI] [PubMed] [Google Scholar]
  24. Tsujimoto Y., Yunis J., Onorato-Showe L., Erikson J., Nowell P. C., Croce C. M. Molecular cloning of the chromosomal breakpoint of B-cell lymphomas and leukemias with the t(11;14) chromosome translocation. Science. 1984 Jun 29;224(4656):1403–1406. doi: 10.1126/science.6610211. [DOI] [PubMed] [Google Scholar]
  25. Woda B. A., Knowles D. M., 2nd Nodular lymphocytic lymphoma eventuating into diffuse histiocytic lymphoma: immunoperoxidase demonstration of monoclonality. Cancer. 1979 Jan;43(1):303–307. doi: 10.1002/1097-0142(197901)43:1<303::aid-cncr2820430144>3.0.co;2-y. [DOI] [PubMed] [Google Scholar]
  26. Wood G. S., Warnke R. A. The immunologic phenotyping of bone marrow biopsies and aspirates: frozen section techniques. Blood. 1982 May;59(5):913–922. [PubMed] [Google Scholar]
  27. Yelton D. E., Scharff M. D. Mutant monoclonal antibodies with alterations in biological functions. J Exp Med. 1982 Oct 1;156(4):1131–1148. doi: 10.1084/jem.156.4.1131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Yunis J. J., Oken M. M., Kaplan M. E., Ensrud K. M., Howe R. R., Theologides A. Distinctive chromosomal abnormalities in histologic subtypes of non-Hodgkin's lymphoma. N Engl J Med. 1982 Nov 11;307(20):1231–1236. doi: 10.1056/NEJM198211113072002. [DOI] [PubMed] [Google Scholar]
  29. Yunis J. J. The chromosomal basis of human neoplasia. Science. 1983 Jul 15;221(4607):227–236. doi: 10.1126/science.6336310. [DOI] [PubMed] [Google Scholar]
  30. van Dongen J. J., Hooijkaas H., Michiels J. J., Grosveld G., de Klein A., van der Kwast T. H., Prins M. E., Abels J., Hagemeijer A. Richter's syndrome with different immunoglobulin light chains and different heavy chain gene rearrangements. Blood. 1984 Aug;64(2):571–575. [PubMed] [Google Scholar]
  31. van den Tweel J. G., Lukes R. J., Taylor C. R. Pathophysiology of lymphocyte transformation. A study of so-called composite lymphomas. Am J Clin Pathol. 1979 May;71(5):509–520. doi: 10.1093/ajcp/71.5.509. [DOI] [PubMed] [Google Scholar]

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