Abstract
The LAZ3 gene has been identified on chromosome band 3q27, which is the breakpoint of reciprocal chromosome translocations observed in B‐cell non‐Hodgkin's lymphoma (NHL). Although the translocations affect various chromosome sites including the immunoglobulin gene loci, molecular studies have indicated that the breakages are clustered within a 10‐kb‐long major translocation cluster region (MTC) at band 3q27. In the current study, we have used a genomic probe from the MTC to study 51 Japanese patients having B‐cell neoplasms with regard to rearrangement of LAZ3. The study detected rearrangement in 12 cases out of 51; the rearrangements occurred within a limited region close to the first exon of the LAZ3 gene. Eight cases out of 12 with rearrangement had diffuse large cell NHL and the immunoblastic variant, including one case transformed from a follicular lymphoma carrying the BCL2 rearrangement. However, the rearrangement was also identified in two NHL patients showing a follicular growth pattern, in one case with indolent chronic lymphocytic leukemia and in one case with high‐grade small noncleaved cell lymphoma with a bulky abdominal mass. Cytogenetic analysis revealed t(3;14)(q27;q32) in 2 cases, t(3;22)(q27;q11) in 3, and a newly identified translocation t(3;6)(q27;p21) in one case. LAZ3 expression was demonstrated in cells carrying the LAZ3 rearrangement, suggesting transcriptional deregulation of the gene. Our results are compatible with previous cytogenetic reports in which the 3q27 translocation was observed in 15–20% of NHL; however, patients with the LAZ3 rearrangements exhibited a wide range of clinico‐pathologic characteristics. Thus, there is no clear consistent association of the 3q27 translocation with a specific subtype of B‐cell neoplasm.
Keywords: 3q27 translocation, LAZ3 gene, Major translocation cluster region, B‐cell neoplasm
Full Text
The Full Text of this article is available as a PDF (539.7 KB).
REFERENCES
- 1. ) Yunis , J. J. , Oken , M. M. , Theologides , A. , Howe , R. B. and Kaplan , M. E.Recurrent chromosomal defects are found in most patients with non‐Hodgkin's lymphoma . Cancer Genet. Cytogenet. , 13 , 17 – 28 ( 1984. ). [DOI] [PubMed] [Google Scholar]
- 2. ) Bloomfield , C. D. , Arthur , D. C. , Frizzera , G. , Levine , E. G. , Peterson , B. A. and Gaji‐Peczalska , K. J.Non‐random chromosome abnormalities in lymphoma . Cancer Res. , 43 , 2975 – 2984 ( 1983. ). [PubMed] [Google Scholar]
- 3. ) Konduru , P. R. K. , Filippa , D. A. , Richardson , M. E. , Jhanwar , S. C. , Chaganti , S. R. , Koziner , B. , Clarkson , B. D. , Lieberman , P. H. and Chaganti , R. S. K.Cytogenetic and histologic correlations in malignant lymphoma . Blood , 69 , 97 – 102 ( 1987. ). [PubMed] [Google Scholar]
- 4. ) Nowell , P. C. and Croce , C. M.Chromosome translocations and oncogenes in human lymphoid tumors . Am. J. Clin. Pathol. , 94 , 229 – 237 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 5. ) Tsujimoto , Y. , Cossman , J. , Jaffe , E. and Croce , C. M.Involvement of the bcl‐2 gene in human follicular lymphoma . Science , 228 , 1440 – 1443 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 6. ) Ohno , H. , Takimoto , G. and McKeithan , T. W.The candidate proto‐oncogene bcl‐3 is related to genes implicated in cell lineage determination and cell cycle control . Cell , 60 , 991 – 997 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 7. ) Offit , K. , Jhanwar , S. , Ebrahim , S. A. D. , Filippa , D. , Clarkson , B. D. and Chaganti , R. S. K.t(3;22)(q27;q11): a novel translocation associated with diffuse non‐Hodgkin's lymphoma . Blood , 74 , 1876 – 1879 ( 1989. ). [PubMed] [Google Scholar]
- 8. ) Leroux , D. , Stul , M. , Sotto , J. J. , Bastard , C. , Couderc , P. , Bensa , J. C. , Monteil , M. , Cassiman , J. J. and Jalbert , P.Translocation t(3;22)(q23;q11) in three patients with diffuse large B‐cell lymphoma . Leukemia , 4 , 373 – 376 ( 1990. ). [PubMed] [Google Scholar]
- 9. ) Bastard , C. , Tilly , H. , Lenormand , B. , Bigorgne , C. , Boulet , D. , Kunlin , A. , Monconduit , M. and Piguet , H.Translocations involving band 3q27 and Ig gene regions in non‐Hodgkin's lymphoma . Blood , 79 , 2527 – 2531 ( 1992. ). [PubMed] [Google Scholar]
- 10. ) Deweindt , C. , Kerckaert , J.‐P. , Tilly , H. , Quief , S. , Nguyen , V. C. and Bastard , C.Cloning of a breakpoint cluster region at band 3q27 involved in human non‐Hodgkin's lymphoma . Genes Chromosomes Cancer , 8 , 149 – 154 ( 1993. ). [DOI] [PubMed] [Google Scholar]
- 11. ) Kerckaert , J.‐P. , Deweindt , C. , Tilly , H. , Quief , S. , Lecocq , G. and Bastard , C.LAZ3, a novel zinc‐finger encoding gene, is disrupted by recurring chromosome 3q27 translocations in human lymphomas . Nat. Genet. , 5 , 66 – 70 ( 1993. ). [DOI] [PubMed] [Google Scholar]
- 12. ) Miki , T. , Fukuda , T. , Nakamura , N. , Arai , A. , Kawamata , N. , Toyota , S. , Tasuga , Y. , Sugahara , Y. , Koyama , T. , Nakamura , Y. , Miura , O. , Katoh , A. , Hirosawa , S. and Aoki , N.Molecular characterization of B cell malignancy with chromosomal translocation involving 3q27 . Int. J. Hematol. , 57 ( Suppl. ), 137 ( 1993. ). [Google Scholar]
- 13. ) Ye , B. H. , Lista , F. , Lo Coco , F. , Knowles , D. M. , Offit , K. , Chaganti , R. S. K. and Dalla‐Favera , R.Alterations of a zinc finger‐encoding gene, BCL6, in diffuse large‐cell lymphoma . Science , 262 , 747 – 750 ( 1993. ). [DOI] [PubMed] [Google Scholar]
- 14. ) The Non‐Hodgkin's Lymphoma Pathologic Classification Project . National Cancer Institute sponsored study of classifications of non‐Hodgkin's lymphomas: summary and description of a working formulation for clinical usage . Cancer , 49 , 2112 – 2135 ( 1982. ). [DOI] [PubMed] [Google Scholar]
- 15. ) Jaffe , E. S. , Raffeld , M. , Medeiros , J. and Stetler‐Stevenson , M.An overview of the classification of non‐Hodgkin's lymphomas: an integration of morphological and phenotypical concepts . Cancer Res. ( Suppl. ), 52 , 5447s – 5452s ( 1992. ). [PubMed] [Google Scholar]
- 16. ) ISCN . “ An International System for Human Cytogenetic Nomenclature ,” ed. Harnden D. G. and Klinger H. P. , published in collaboration with Cytogenet . Cell Genet . ( 1985. ). Karger; , Barsel . [Google Scholar]
- 17. ) Takahashi , N. , Nakai , S. and Honjo , T.Cloning of human immunoglobulin μ gene and comparison with mouse μ gene . Nucleic Acids Res. , 8 , 5983 – 5991 ( 1980. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18. ) Ohno , H. , Akasaka , T. , Ohmura , K. , Nakamura , T. , Gohma , I. , Masuya , M. , Amano , H. , Imanaka , T. and Ohno , Y.Non‐Hodgkin's lymphomas with chromosomal translocations involving 3q27 band and immunoglobulin gene loci: report of two cases . Cancer Genet. Cytogenet. , 72 , 33 – 38 ( 1994. ). [DOI] [PubMed] [Google Scholar]
- 19. ) Rai , K. R. , Sawitsky , A. , Cronkite , E. P. , Chanana , A. D. , Levy , R. N. and Pasternak , B. S.Clinical staging of chronic lymphocytic leukemia . Blood , 46 , 219 – 234 ( 1975. ). [PubMed] [Google Scholar]
- 20. ) Fifth International Workshop on Chromosomes in Leukemia‐Lymphoma . Correlation of chromosome abnormalities with histologic and immunologic characteristics in non‐Hodgkin's lymphoma and adult T cell leukemia‐lymphoma . Blood , 70 , 1554 – 1564 ( 1987. ). [PubMed] [Google Scholar]
- 21. ) Kaneko , Y. , Rowley , J. D. , Variakojis , D. , Haren , J. M. , Ueshima , Y. , Daly , K. and Kluskens , L. F.Prognostic implications of karyotype and morphology in patients with non‐Hodgkin's lymphoma . Int. J. Cancer , 32 , 683 – 692 ( 1983. ). [DOI] [PubMed] [Google Scholar]
- 22. ) Konishi , H. , Sakurai , M. , Nakao , H. , Maseki , N. , Kaneko , Y. , Yagiri , Y.Notohara , K. and Frizzera , G.Chromosome abnormalities in malignant lymphoma in patients from Kurashiki: histological and immunophenotypic correlations . Cancer Res. , 50 , 2698 – 2703 ( 1990. ). [PubMed] [Google Scholar]
- 23. ) Takeuchi , J. , Ochi , H. , Han , T. , Ozer , H. , Henderson , E. S. and Sandberg , A. A.Clonal chromosome abnormalities in prison‐acquired lymphoproliferative syndrome . Cancer Genet. Cytogenet. , 15 , 7 – 16 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 24. ) Slavutsky , I. , de Vinuesa , M. L. , Larripa , I. , Dupont , J. and de Salum , S. B.Translocation (2;3) in hematologic malignancies . Cancer Genet. Cytogenet. , 21 , 335 – 342 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 25. ) Raffeld , M. and Jaffe , E. S.bcl‐1, t(11;14), and mantle cell‐derived lymphomas . Blood , 78 , 259 – 263 ( 1991. ). [PubMed] [Google Scholar]
- 26. ) Thangavelu , M. , Olopade , O. , Beckman , E. , Vardiman , J. W. , Larson , R. A. , McKeithan , T. W. , Le Beau , M. M. and Rowley , J. D.Clinical, morphologic, and cytogenetic characteristics of patients with lymphoid malignancies characterized by both t(14;18)(q32;q21) and t(8;14) (q24;q32) or t(8;22)(q24;q11) . Genes Chromosomes Cancer , 2 , 147 – 158 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 27. ) Baron , B. W. , Nucifora , G. , McCabe , N. , Espinosa , R. , III , Le Beau , M. M. and McKeithan , T. W.Identification of the gene associated with the recurring chromosomal translocations t(3;14)(q27;q32) and t(3;22)(q27;q11) in B‐cell lymphomas . Proc. Natl. Acad. Sci. USA , 90 , 5262 – 5266 ( 1993. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28. ) Ye , B. H. , Rao , P. H. , Chaganti , R. S. K. and Dalla‐Favera , R.Cloning of bcl‐6, the locus involved in chromosome translocations affecting band 3q27 in B‐cell lymphoma . Cancer Res. , 53 , 2732 – 2735 ( 1993. ). [PubMed] [Google Scholar]
- 29. ) Adachi , M. , Tefferi , A. , Greipp , P. R. , Kipps , T. J. and Tsujimoto , Y.Preferential linkage of bcl‐2 to immunoglobulin light chain gene in chronic lymphocytic leukemia . J. Exp. Med. , 171 , 559 – 564 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30. ) Kakizuka , A. , Miller , W. H. , Umesono , K. , Warrell , R. P. , Frankel , S. R. , Murty , V. V. V. S. , Dmitrovsky , E. and Evans , R. M.Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RARα with a novel putative transcription factor, PML . Cell , 66 , 663 – 674 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 31. ) Tkachuk , D. C. , Kohler , S. and Cleary , M. L.Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias . Cell , 71 , 691 – 700 ( 1992. ). [DOI] [PubMed] [Google Scholar]