The t(14;18) chromosome translocations involved in B-cell neoplasms result from mistakes in VDJ joining.

In this study, the joining sequences between chromosomes 14 and 18 on the 14q+ chromosomes of a patient with pre-B-cell leukemia and four patients with follicular lymphoma carrying a t(14;18) chromosome translocation were analyzed. In each case, the involved segment of chromosome 18 has recombined with the immunoglobulin heavy-chain joining segment (JH) on chromosome 14. The sites of the recombination on chromosome 14 are located close to the 5' end of the involved JH segment, where the diversity (D) regions are rearranged with the JH segments in the production of active heavy-chain genes. As extraneous nucleotides (N regions) were observed at joining sites and specific signal-like sequences were detected on chromosome 18 in close proximity to the breakpoints, it is concluded that the t(14;18) chromosome translocation is the result of a mistake during the process of VDJ joining at the pre-B-cell stage of differentiation. The putative recombinase joins separated DNA segments on two different chromosomes instead of joining separated segments on the same chromosome, causing a t(14;18) chromosome translocation in the involved B cells.

[1]  Y. Tsujimoto,et al.  Involvement of the bcl-2 gene in human follicular lymphoma. , 1985, Science.

[2]  P. Nowell,et al.  Clustering of breakpoints on chromosome 11 in human B-cell neoplasms with the t(11 ; 14) chromosome translocation , 1985, Nature.

[3]  R. Warnke,et al.  Epstein-Barr virus-associated B-cell proliferations of diverse clonal origins after bone marrow transplantation in a 12-year-old patient with severe combined immunodeficiency. , 1985, The New England journal of medicine.

[4]  C. Croce,et al.  Coexpression of translocated and normal c-myc oncogenes in hybrids between Daudi and lymphoblastoid cells. , 1985, Science.

[5]  A. Palumbo,et al.  Gene for alpha-chain of human T-cell receptor: location on chromosome 14 region involved in T-cell neoplasms. , 1985, Science.

[6]  P. Nowell,et al.  Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. , 1984, Science.

[7]  David Baltimore,et al.  Insertion of N regions into heavy-chain genes is correlated with expression of terminal deoxytransferase in B cells , 1984, Nature.

[8]  J. Sklar,et al.  LYMPHOPROLIFERATIVE DISORDERS IN CARDIAC TRANSPLANT RECIPIENTS ARE MULTICLONAL LYMPHOMAS , 1984, The Lancet.

[9]  P. Nowell,et al.  Molecular cloning of the chromosomal breakpoint of B-cell lymphomas and leukemias with the t(11;14) chromosome translocation. , 1984, Science.

[10]  C. Mecucci,et al.  High incidence of chromosome abnormalities in IgG3 myeloma. , 1984, Cancer genetics and cytogenetics.

[11]  S. Tonegawa.  Somatic generation of antibody diversity , 1983, Nature.

[12]  R. R. Howe,et al.  Distinctive chromosomal abnormalities in histologic subtypes of non-Hodgkin's lymphoma. , 1982, The New England journal of medicine.

[13]  J. Rowley,et al.  Identification of the constant chromosome regions involved in human hematologic malignant disease. , 1982, Science.

[14]  Ulrich Siebenlist,et al.  Structure of the human immunoglobulin μ locus: Characterization of embryonic and rearranged J and D genes , 1981, Cell.

[15]  J. Rowley,et al.  Chromosome abnormalities in poorly differentiated lymphocytic lymphoma. , 1979, Cancer research.

[16]  H. Berghe,et al.  A new characteristic karyotypic anomaly in lymphoproliferative disorders , 1979, Cancer.

[17]  H. Koprowski,et al.  Chromosomal location of the genes for human immunoglobulin heavy chains. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[18]  B. Woda,et al.  Nodular lymphocytic lymphoma eventuating into diffuse histiocytic lymphoma. Immunoperoxidase demonstration of monoclonality , 1979, Cancer.

[19]  E. Jaffe,et al.  Immunologic aspects and pathology of the malignant lymphomas , 1978, Cancer.

[20]  G. Klein,et al.  Characteristic chromosomal abnormalities in biopsies and lymphoid‐cell lines from patients with burkitt and non‐burkitt lymphomas , 1976, International journal of cancer.