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Novel genomic imbalances and chromosome translocations involving c-myc gene in Burkitt's lymphoma

Leukemia volume 15, pages 1582–1588 (2001)Cite this article

Abstract

In this study, CA46 and ST486, two Epstein–Barr (EBV) negative cell lines derived from sporadic BL, were analyzed by multicolor spectral karyotyping, G-banding, fluorescence in situ hybridization with single-copy gene probes, and comparative genomic hybridization (CGH). In addition to reciprocal t(8;14)(q24;q32) translocation involving c-myc and IgH loci, we identified a t(7;8;14)(q11.2;q24;q32) translocation in CA 46 cells and t(8;14;18)(q24;q32;q23) in ST486 cells. Both rearrangements were not previously described in BL and resulted in transposition of myc sequences in a new genomic configuration. Several DNA imbalances mapped by CGH at the same sites in both lines, may reflect recurrent genomic changes that are relevant to pathogenesis of BL. We tested the tumorigenicity of these lines by injecting cells intraperitoneally in SCID mice. In two separate experiments, CA46 cells produced tumors 2 weeks after cell inoculation while ST486 cells induced only one tumor after a long latency period. Partial duplication of the long arm of chromosome 1 involving variable bands but always band 1q23 is the second most common alteration in BL and is known to be associated with aggressive tumors and poor prognosis. Duplication of the bands 1q23–24 commonly observed in EBV-negative lines was identified only in highly tumorigenic CA46 cells suggesting that this region harbor gene(s) associated with tumor cell invasiveness.

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References

  1. Mitelman F, Mertens F, Johansson B . A breakpoint map of recurrent chromosomal rearrangements in human neoplasia Nat Genet 1997 15: 417–474

    Article  CAS  PubMed  Google Scholar 

  2. Nowell P, Dalla-Favera R, Finan J, Erikson J, Croce C . Chromosome translocations, immunoglobulin genes, and neoplasia In: Rowley JD, Ultmann JE (eds) Chromosomes and Cancer: from Molecules to Man Academic Press: New York 1983 pp 165–181

    Google Scholar 

  3. Bishop JM . The molecular genetics of cancer Science 1987 235: 305–311

    Article  CAS  PubMed  Google Scholar 

  4. Cleary ML . Oncogenic conversion of transcription factors by chromosomal translocations Cell 1991 66: 619–622

    Article  CAS  PubMed  Google Scholar 

  5. Rabbitts TH . Chromosomal translocations in human cancer Nature 1994 372: 143–149

    Article  CAS  PubMed  Google Scholar 

  6. Kallioniemi A, Kallioniemi OP, Sudar D, Rutovitz D, Gray JW, Waldman F, Pinkel D . Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors Science 1992 258: 818–821

    Article  CAS  PubMed  Google Scholar 

  7. Schröck E, du Manoir S, Veldman T, Schoell B, Wienberg J, Ferguson-Smith MA, Ning Y, Ledbetter DH, Bar-Am I, Soenksen D, Garini Y, Ried, T . Multicolor spectral karyotyping of human chromosomes Science 1996 273: 494–497

    Article  PubMed  Google Scholar 

  8. Dalla-Favera R, Bregni M, Erikson J, Patterson D, Gallo RC, Croce CM . Human c-myc onc gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells Proc Natl Acad Sci USA 1982 79: 7824–7827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Pelicci PG, Knowles DMD, Magrath I, Dalla-Favera R . Chromosomal breakpoints and structural alterations of the c-myc locus differ in endemic and sporadic forms of Burkitt lymphoma Proc Natl Acad Sci USA 1986 83: 2984–2988

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Showe LC, Ballantine M, Nishikura K, Erikson J, Kaji H, Croce CM . Cloning and sequencing of a c-myc oncogene in a Burkitt's lymphoma cell line that is translocated to a germ line alpha switch region Mol Cell Biol 1985 5: 501–509

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Zimonjic DB, Pollock J, Westerfield P, Popescu NC, Ley JT . Acquired, non-random chromosomal abnormlities associated with the development of acute promyelocitic leukemia in transgenic mice Proc Natl Acad Sci USA 2000 97: 13306–13311

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Zimonjic DB, Rezanka L, DiPaolo JA, Popescu NC . Refined localization of the erbB-3 proto-oncogene by direct visualization of FISH signals on LUT-inverted and contrast-enhanced digital images of DAPI-banded chromosomes Cancer Genet Cytogenet 1995 80: 100–102

    Article  CAS  PubMed  Google Scholar 

  13. Honjo T, Matsuda F . Immunoglobulin heavy chain loci of mouse and human In: Honjo T, Frederick W (eds) Immunoglobulin Genes 2nd edn Academic Press: London 1995 pp 145–171

    Chapter  Google Scholar 

  14. Veldman T, Vignon C, Schrock E, Rowley JD, Ried T . Hidden chromosome abnormalities in haematological malignancies detected by multicolour spectral karyotyping Nat Genet 1997 15: 406–410

    Article  CAS  PubMed  Google Scholar 

  15. Vazquez-Mazariego Y, Cabello P, Garcia-Sagredo JM, Lopez-Yarto A, Vallcorba I, Resino M, Munoz R, Perez I, Mayayo M, Ferro MT . Burkitt lymphoma with a duplication of der(8)t(2;8). Interpretation of a complex karyotype by chromosome painting Cancer Genet Cytogenet 1994 76: 136–139

    Article  CAS  PubMed  Google Scholar 

  16. Khaira P, James CD, Leffak M . Amplification of the translocated c-myc genes in three Burkitt lymphoma cell lines Gene 1998 211: 101–108

    Article  CAS  PubMed  Google Scholar 

  17. Werner CA, Dohner H, Joos S, Trumper LH, Baudis M, Barth FE, Ott G, Moller P, Bentz M . High-level DNA amplifications are common genetic aberrations in B-cell neoplasms Am J Pathol 1997 151: 335–342

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Zunino A, Viaggi S, Ottaggio L, Fronza G, Schenone A, Roncella S, Abbondandolo A . Chromosomal aberrations evaluated by CGH, FISH and GTG-banding in a case of AIDS-related Burkitt's lymphoma Haematologica 2000 85: 250–255

    CAS  PubMed  Google Scholar 

  19. Ried T, Heselmeyer-Haddad K, Blegen H, Schrock E, Auer G . Genomic changes defining the genesis, progression, and malignancy potential in solid human tumors: a phenotype/genotype correlation Genes Chromos Cancer 1999 25: 195–204

    Article  CAS  PubMed  Google Scholar 

  20. Zimonjic DB, Keck-Waggoner CL, Yuan BZ, Kraus MH, Popescu NC . Profile of genetic alterations and tumorigenicity of human breast cancer cells Int J Oncol 2000 16: 221–230

    CAS  PubMed  Google Scholar 

  21. Bloomfield CD, Arthur DC, Frizzera G, Levine EG, Peterson BA, Gajl-Peczalska KJ . Nonrandom chromosome abnormalities in lymphoma Cancer Res 1983 43: 2975–2984

    CAS  PubMed  Google Scholar 

  22. Sandberg AA, Chen Z . Cancer cytogenetics and molecular genetics: clinical implications Int J Oncol 1995 7: 1241–1251

    CAS  PubMed  Google Scholar 

  23. Sheer D, Squire J . Clinical applications of genetic rearrangements in cancer Semin Cancer Biol 1996 7: 25–32

    Article  CAS  PubMed  Google Scholar 

  24. Douglass EC, Magrath IT, Lee EC, Whang-Peng J . Cytogenetic studies in non-African Burkitt lymphoma Blood 1980 55: 148–155

    Article  CAS  PubMed  Google Scholar 

  25. Berger R, Le Coniat M, Derre J, Vecchione D . Secondary nonrandom chromosomal abnormalities of band 13q34 in Burkitt lymphoma–leukemia Genes Chromos Cancer 1989 1: 115–118

    Article  CAS  PubMed  Google Scholar 

  26. Kornblau SM, Goodacre A, Cabanillas F . Chromosomal abnormalities in adult non-endemic Burkitt's lymphoma and leukemia: 22 new reports and a review of 148 cases from the literature Hematol Oncol 1991 9: 63–78

    Article  CAS  PubMed  Google Scholar 

  27. Offit K, Jhanwar SC, Ladanyi M, Filippa DA, Chaganti RS . Cytogenetic analysis of 434 consecutively ascertained specimens of non-Hodgkin's lymphoma: correlations between recurrent aberrations, histology, and exposure to cytotoxic treatment Genes Chromos Cancer 1991 3: 189–201

    Article  CAS  PubMed  Google Scholar 

  28. Polito P, Cilia AM, Gloghini A, Cozzi M, Perin T, De Paoli P, Gaidano G, Carbone A . High frequency of EBV association with non-random abnormalities of the chromosome region 1q21–25 in AIDS-related Burkitt's lymphoma-derived cell lines Int J Cancer 1995 61: 370–374

    Article  CAS  PubMed  Google Scholar 

  29. Berger R, Bernheim A . Is there a functional equivalence between abnormalities of the long arm of chromosome 1 and the presence of Epstein–Barr virus in continuous lines of Burkitt's lymphoma? CR Acad Sci III 1984 298: 143–145

    CAS  Google Scholar 

  30. Gurtsevitch VE, O'Conor GT, Lenoir GM . Burkitt's lymphoma cell lines reveal different degrees of tumorigenicity in nude mice Int J Cancer 1988 41: 87–95

    Article  CAS  PubMed  Google Scholar 

  31. Chaganti RS, Balazs I, Jhanwar SC, Murty VV, Koduru PR, Grzeschik KH, Stavnezer E . The cellular homologue of the transforming gene of SKV avian retrovirus maps to human chromosome region 1q22-q24 Cytogenet Cell Genet 1986 43: 181–186

    Article  CAS  PubMed  Google Scholar 

  32. Morris CM, Hao QL, Heisterkamp N, Fitzgerald PH, Groffen J . Localization of the TRK proto-oncogene to human chromosome bands 1q23–1q24 Oncogene 1991 6: 1093–1095

    CAS  PubMed  Google Scholar 

  33. Engelkamp D, Schafer BW, Mattei MG, Erne P, Heizmann CW . Six S100 genes are clustered on human chromosome 1q21: identification of two genes coding for the two previously unreported calcium-binding proteins S100D and S100E Proc Natl Acad Sci USA 1993 90: 6547–6551

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Willis TG, Zalcberg IR, Coignet LJ, Wlodarska I, Stul M, Jadayel DM, Bastard C, Treleaven JG, Catovsky D, Silva ML, Dyer MJ . Molecular cloning of translocation t(1;14)(q21;q32) defines a novel gene (BCL9) at chromosome 1q21 Blood 1998 91: 1873–1881

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Dr Douglas Kingma from the Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland, for histological diagnosis of the tumors.

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  1. Division of Basic Sciences, Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD, USA

    DB Zimonjic, C Keck-Waggoner & NC Popescu

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Zimonjic, D., Keck-Waggoner, C. & Popescu, N. Novel genomic imbalances and chromosome translocations involving c-myc gene in Burkitt's lymphoma. Leukemia 15, 1582–1588 (2001). https://doi.org/10.1038/sj.leu.2402281

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