Refinement of lymphoma cytogenetics by the chromosome 18q21 major breakpoint region.

A small (2.8-kilobase, kb) major breakpoint region localized to segment 18q21 rearranges in greater than 70% of t(14;18)(q32;q21) lymphomas. This rearrangement interrupts the Bcl-2 gene and introduces it into the Ig locus at 14q32. The rearrangement between the joining region (JH) of Ig on chromosome 14 and the 18q21 region creates a translocation-specific DNA rearrangement. We generated probes that distinguish the 14;18 juncture on the derivative (der) 14 and der (18) chromosomes, providing a molecular approach to t(14;18) identification. Approximately 60% of unselected follicular lymphomas, 20% of diffuse large cell lymphomas, and 50% of adult undifferentiated non-Burkitt lymphomas demonstrated 14;18 rearrangements within the major breakpoint region. Examination of DNA for 14;18 rearrangements resolved the identity of 14q+ chromosomes in two patient's cells that lacked an obvious reciprocal partner. Identification of the exact restriction fragments that mediate translocations complements routine cytogenetics. The detection of DNA rearrangements does not require dividing cells or the presence of an identifiable reciprocal partner and can detect clonal translocation rearrangements when the neoplastic cells are only a minority of all cells present.

[1]  S. Korsmeyer,et al.  Expression of Bcl-2 and Bcl-2-Ig fusion transcripts in normal and neoplastic cells. , 1987, The Journal of clinical investigation.

[2]  S. Korsmeyer,et al.  Mechanism of the t(14;18) chromosomal translocation: structural analysis of both derivative 14 and 18 reciprocal partners. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[3]  C. Croce,et al.  DNA rearrangements in human follicular lymphoma can involve the 5' or the 3' region of the bcl-2 gene. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[4]  M. Oken,et al.  Multiple recurrent genomic defects in follicular lymphoma. A possible model for cancer. , 1987, The New England journal of medicine.

[5]  J. Sklar,et al.  Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation , 1986, Cell.

[6]  J. Sklar,et al.  Detection of a second t(14;18) breakpoint cluster region in human follicular lymphomas , 1986, The Journal of experimental medicine.

[7]  Y. Tsujimoto,et al.  Analysis of the structure, transcripts, and protein products of bcl-2, the gene involved in human follicular lymphoma. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[8]  J. Sklar,et al.  Nucleotide sequence of a t(14;18) chromosomal breakpoint in follicular lymphoma and demonstration of a breakpoint-cluster region near a transcriptionally active locus on chromosome 18. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[9]  C. Croce,et al.  The t(14;18) chromosome translocations involved in B-cell neoplasms result from mistakes in VDJ joining. , 1985, Science.

[10]  P. Nowell,et al.  Locus of the alpha-chain of the T-cell receptor is split by chromosome translocation in T-cell leukemias. , 1985, Science.

[11]  S. Korsmeyer,et al.  Cloning the chromosomal breakpoint of t(14;18) human lymphomas: clustering around Jh on chromosome 14 and near a transcriptional unit on 18 , 1985, Cell.

[12]  C. Bloomfield,et al.  There are differences in cytogenetic abnormalities among histologic subtypes of the non-Hodgkin's lymphomas. , 1985, Blood.

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

[14]  E. Jaffe,et al.  Immunologic phenotypes of diffuse, aggressive, non‐Hodgkin's lymphomas. Correlation with clinical features , 1984, Cancer.

[15]  M. Olson,et al.  Separation of chromosomal DNA molecules from yeast by orthogonal-field-alternation gel electrophoresis. , 1984, Nucleic acids research.

[16]  D. Schwartz,et al.  Separation of yeast chromosome-sized DNAs by pulsed field gradient gel electrophoresis , 1984, Cell.

[17]  J. Yunis.  The chromosomal basis of human neoplasia. , 1983, Science.

[18]  A. Feinberg,et al.  A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. , 1983, Analytical biochemistry.

[19]  C. Bloomfield,et al.  Nonrandom chromosome abnormalities in lymphoma. , 1983, Cancer research.

[20]  C. Croce,et al.  Translocation and rearrangements of the c-myc oncogene locus in human undifferentiated B-cell lymphomas. , 1983, Science.

[21]  P. Leder,et al.  Translocation of the c-myc gene into the immunoglobulin heavy chain locus in human Burkitt lymphoma and murine plasmacytoma cells. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[22]  R. Berger,et al.  Correlation between immunoglobulin light chain expression and variant translocation in Burkitt's lymphoma , 1982, Nature.

[23]  P. Leder,et al.  Human immunoglobulin heavy chain genes map to a region of translocations in malignant B lymphocytes. , 1982, Science.

[24]  National Cancer Institute sponsored study of classifications of non-Hodgkin's lymphomas: summary and description of a working formulation for clinical usage. The Non-Hodgkin's Lymphoma Pathologic Classification Project. , 1982, Cancer.

[25]  C. Osborne,et al.  Histologic progression in non-Hodgkin's lymphoma. , 1982, Blood.

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

[27]  G. Klein.  The role of gene dosage and genetic transpositions in carcinogenesis , 1981, Nature.

[28]  A. Sandberg.  Chromosome changes in the lymphomas. , 1981, Human pathology.

[29]  G R Stark,et al.  Detection of specific RNAs or specific fragments of DNA by fractionation in gels and transfer to diazobenzyloxymethyl paper. , 1979, Methods in enzymology.

[30]  Henry Rappaport,et al.  Follicular lymphoma. A re‐evaluation of its position in the scheme of malignant lymphoma based on a survey of 253 cases , 1956 .