Abstract
Although follicle center cell (FCC) lymphomas represent mature B cells, a considerable percentage do not have detectable Ig production. We have used Southern blotting and the polymerase chain reaction (PCR) to study the involvement of translocations t(14;18) and t(8;14) in causing defective Ig production in 16 Ig- FCC-derived lymphomas and three Ig- B cell acute lymphoblastic leukemias. In 6 of 19 cases, a t(14;18) was present with the other allele either deleted or in germline. In two cases a t(14;18) and a t(8;14) affected both Ig alleles, as confirmed by karyotyping. In two other cases, rearrangement of both bcl-2 on chromosome 18 and c-myc on chromosome 8 were found as well. Although cytogenetic proof was not available, the latter was probably involved in t(8;14). Restriction map analysis of one more case showed rearrangement on the pseudo-JH3 gene on one allele and t(14;18) on the other. Thus, in 11 of 19 cases, defective Ig H chain production could be explained by the inactivation of both Ig H chain genes due to translocation of one allele, in combination with deletions or defective rearrangements of the other allele. In contrast, in 28 of 30 Ig+ lymphomas, one functional Ig H chain allele was found, either in, or not in, combination with t(14;18). In two cases a single rearranged Ig H chain allele was found in combination with rearrangement of bcl-2. No comigration of the single Ig rearrangement with bcl-2, however, was found both by Southern blotting and PCR, suggesting a variant bcl-2 translocation, which leaves the Ig H chain allele functionally intact.
Full Text
The Full Text of this article is available as a PDF (769.6 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- De Jong D., Voetdijk B. M., Beverstock G. C., van Ommen G. J., Willemze R., Kluin P. M. Activation of the c-myc oncogene in a precursor-B-cell blast crisis of follicular lymphoma, presenting as composite lymphoma. N Engl J Med. 1988 May 26;318(21):1373–1378. doi: 10.1056/NEJM198805263182106. [DOI] [PubMed] [Google Scholar]
- Garcia C. F., Warnke R. A., Weiss L. M. Follicular large cell lymphoma. An immunophenotype study. Am J Pathol. 1986 Jun;123(3):425–431. [PMC free article] [PubMed] [Google Scholar]
- Haluska F. G., Finver S., Tsujimoto Y., Croce C. M. The t(8; 14) chromosomal translocation occurring in B-cell malignancies results from mistakes in V-D-J joining. Nature. 1986 Nov 13;324(6093):158–161. doi: 10.1038/324158a0. [DOI] [PubMed] [Google Scholar]
- Higuchi R., von Beroldingen C. H., Sensabaugh G. F., Erlich H. A. DNA typing from single hairs. Nature. 1988 Apr 7;332(6164):543–546. doi: 10.1038/332543a0. [DOI] [PubMed] [Google Scholar]
- Kluin-Nelemans H. C., Gmelig-Meyling F. H., Kootte A. M., den Ottolander G. J., Termijtelen A., Kluin P. M., Beverstock G. C., Brand A. T-cell prolymphocytic leukemia with an unusual phenotype CD4+ CD8+. Cancer. 1987 Aug 15;60(4):794–803. doi: 10.1002/1097-0142(19870815)60:4<794::aid-cncr2820600415>3.0.co;2-r. [DOI] [PubMed] [Google Scholar]
- Lee M. S., Blick M. B., Pathak S., Trujillo J. M., Butler J. J., Katz R. L., McLaughlin P., Hagemeister F. B., Velasquez W. S., Goodacre A. The gene located at chromosome 18 band q21 is rearranged in uncultured diffuse lymphomas as well as follicular lymphomas. Blood. 1987 Jul;70(1):90–95. [PubMed] [Google Scholar]
- Neri A., Barriga F., Knowles D. M., Magrath I. T., Dalla-Favera R. Different regions of the immunoglobulin heavy-chain locus are involved in chromosomal translocations in distinct pathogenetic forms of Burkitt lymphoma. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2748–2752. doi: 10.1073/pnas.85.8.2748. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ngan B. Y., Chen-Levy Z., Weiss L. M., Warnke R. A., Cleary M. L. Expression in non-Hodgkin's lymphoma of the bcl-2 protein associated with the t(14;18) chromosomal translocation. N Engl J Med. 1988 Jun 23;318(25):1638–1644. doi: 10.1056/NEJM198806233182502. [DOI] [PubMed] [Google Scholar]
- Parslow T. G., Blair D. L., Murphy W. J., Granner D. K. Structure of the 5' ends of immunoglobulin genes: a novel conserved sequence. Proc Natl Acad Sci U S A. 1984 May;81(9):2650–2654. doi: 10.1073/pnas.81.9.2650. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pollok B. A., Anker R., Eldridge P., Hendershot L., Levitt D. Molecular basis of the cell-surface expression of immunoglobulin mu chain without light chain in human B lymphocytes. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9199–9203. doi: 10.1073/pnas.84.24.9199. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rowley J. D. Chromosome studies in the non-Hodgkin's lymphomas: the role of the 14;18 translocation. J Clin Oncol. 1988 May;6(5):919–925. doi: 10.1200/JCO.1988.6.5.919. [DOI] [PubMed] [Google Scholar]
- Siminovitch K. A., Jensen J. P., Epstein A. L., Korsmeyer S. J. Immunoglobulin gene rearrangements and expression in diffuse histiocytic lymphomas reveal cellular lineage, molecular defects, and sites of chromosomal translocation. Blood. 1986 Feb;67(2):391–397. [PubMed] [Google Scholar]
- Tsujimoto Y., Bashir M. M., Givol I., Cossman J., Jaffe E., Croce C. M. DNA rearrangements in human follicular lymphoma can involve the 5' or the 3' region of the bcl-2 gene. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1329–1331. doi: 10.1073/pnas.84.5.1329. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tsujimoto Y., Louie E., Bashir M. M., Croce C. M. The reciprocal partners of both the t(14; 18) and the t(11; 14) translocations involved in B-cell neoplasms are rearranged by the same mechanism. Oncogene. 1988 Apr;2(4):347–351. [PubMed] [Google Scholar]