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Evidence for a new tumour suppressor locus (DBM) in human B–cell neoplasia telomeric to the retinoblastoma gene

Nature Genetics volume 3, pages 67–72 (1993)Cite this article

Abstract

Roughly 25% of human B–cell chronic lymphocytic leukaemias (CLL) are characterized by a chromosomal lesion involving 13q14. This region contains the retinoblastoma gene (RB1). We have used a variety of techniques to determine whether RB1 or some other locus is the critical region in 11 cases of low grade B–cell malignancy (mainly CLL), all with deletions or translocations involving 13q14. In all cases, except the one with minimal disease, there was deletion or a structural lesion in the region of D13S25, with at least 4 cases showing homozyogous disruption. We conclude that D13S25 lies close to a tumour suppressor locus whose inactivation contributes to the initiation or progression of low grade B–cell malignancy. This locus is located at least 530 kilobases telomeric to RB1.

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References

  1. Juliusson, G. et al. Prognostic subgroups in B-cell chronic lymphocytic leukaemia defined by specific chromosomal abnormalities. New. Engl. J. Med. 323, 720–724 (1990).

    Article  CAS  PubMed  Google Scholar 

  2. Weinberg, R.A. The retinoblastoma gene and gene product. Cancer Surveys 12, (eds Levine A.J. & Franks L.M.) 43–57 (Cold Spring Harbor Laboratory Press, New York, 1992).

    Google Scholar 

  3. Marshall, C.J. Tumour suppressor genes. Cell 64, 313–326 (1991).

    Article  CAS  PubMed  Google Scholar 

  4. Friend, S.H. et al. A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 323, 643–646 (1986).

    Article  CAS  PubMed  Google Scholar 

  5. Harbour, J.W. et al. Abnormalities in structure and expression of the human retinoblastoma gene in SCLC. Science 241, 353–357 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. T'Ang, A., Varley, J.M., Chackraborty, S., Murphree, A.L. & Fung, Y.-K.T. Structural rearrangement of the retinoblastoma gene in human breast carcinoma. Science, 242 263–266 (1988).

    Article  CAS  PubMed  Google Scholar 

  7. Oscier, D., Chapman, R., Fitchett, M. & Cowell, J. Deletion of a retinoblastoma gene in B-cell chronic lymphocytic leukaemia. Blood 76, 241 (1990).

    Google Scholar 

  8. Morris, C.M., Cochrane, J.M., Benjes, S.M., Crossen, P.E. & Fitzgerald, P.H. Molecular definition of interstitial deletions of chromosome 13 in leukemic cells. Genes Chr. Cancer 3, 455–460 (1991).

    Article  CAS  Google Scholar 

  9. Liu, Y. et al. Retinoblastoma gene deletions in B-cell chronic lymphocytic leukemia. Genes Chr. Cancer 4, 250–256 (1992).

    Article  CAS  Google Scholar 

  10. Ginsberg, A.M., Raffeld, M., Raffeld, M. & Crossman, J. Inactivation of the retinoblastoma gene in human lymphoid neoplasia. Blood 77, 833–840 (1991).

    CAS  PubMed  Google Scholar 

  11. Furukawa, Y., Ishida, Y., Belvin, M., DeCaprio, J.A. & Griffin, J.D. Abnormalities in expression of the product of the retinoblastoma susceptibility gene in primary human leukemias. Blood 76, 272 (1990).

    Google Scholar 

  12. Abramson, D.H., Ellsworth, R.M., Kitchin, F.D. & Tung, G. Second nonocular tumours in retinoblastoma survivors. Are they radiation-induced? Opthamology 91, 1351–1355 (1984).

    Article  CAS  Google Scholar 

  13. Saltman, D.L. et al. Characterisation of a new non-Hodgkin's lymphoma cell line (NCEB-1) with a chromosomal (11 ;14) translocation t(11 ;14)(q13;q32). Blood 72, 2026–2030 (1988).

    CAS  PubMed  Google Scholar 

  14. Melchers, F., Gother, M. & Warner, N.L. Preface: Lymphocyte Hybridomas. Curr. Top. Microbiol. Immunol. 81, IX–XXII (1978).

    CAS  PubMed  Google Scholar 

  15. Lund, E. et al. UI small nuclear RNA genes are located on human chromosome 1 and are examined in mouse-human hybrid cells. Molec. cell Biol. 3, 2211–2220 (1983).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Human Gene Mapping 11 (1991). Cytogenet. cell Genet. 58, 580–604 (1991).

  17. Lalande, M. et al. Isolation of human chromosome 13-specific DNA sequences cloned from flow sorted chromosomes and potentially linked to the retinoblastoma locus. Cancer Genet. Cytogenet. 13, 283–295 (1984).

    Article  CAS  PubMed  Google Scholar 

  18. Bowcock, A.M. & Herbert, J.M. An Sspl RFLP at the D13S25 locus identified by the anonymous single copy probe H2-42. Nucl. Acids. Res. 18, 7194 (1991).

    Article  Google Scholar 

  19. Wiggs, J. et al. Prediction of the risk of hereditary retinoblastoma using DNA polymorphisms within the retinoblastoma gene. New Engl. J. Med. 318, 151–157 (1988).

    Article  CAS  PubMed  Google Scholar 

  20. Higgins, M.J., Hansen, M.F., Cavenee, W.K. & Lalande, M. Molecular detection of chromosomal translocations that disrupt the putative retinoblastoma susceptibility locus. Molec. cell Biol. 9, 1–5 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ford, G.H., Gallie, B.L., Phillips, R.A. & Becker, A.G. A physical map around the retinoblastoma gene. Genomics 6, 284–292 (1990).

    Article  CAS  PubMed  Google Scholar 

  22. Hansen, M.F., Morgan, R., Sandberg, A.A. & Cavenee, W.K. Structural alterations at the putative retinoblastoma locus. Cancer Genet. Cytogenet. 49, 15–23 (1990).

    Article  CAS  PubMed  Google Scholar 

  23. Cheng, J., Scully, P., Shaw, J.-Y., Lee, W.-H., Vila, V. & Haas, M. Homozygous deletion of the retinoblastoma gene in an acute lymphocytic leukemia (T) cell line. Blood 75, 730–735 (1990).

    CAS  PubMed  Google Scholar 

  24. Chen, Y.-C. et al. Deletion of the human retinoblastoma gene in primary leukemias. Blood 76, 2060–2064 (1990).

    CAS  PubMed  Google Scholar 

  25. Hillion, J., Larsen, C.-J. & Berger, R. Homozygous deletion of the 3′ end of the RB1 gene in a case of Philadelphia positive-acute lymphoblastic leukemia. Cancer Genet. Cytogenet 54, 197–203 (1991).

    Article  CAS  PubMed  Google Scholar 

  26. Ross, F.M. & Stockdill, G. Clonal chromosome abnormalities in chronic lymphocytic leukaemia patients revealed by TPA stimulation of whole blood culture. Cancer Genet. Cytogenet. 25, 109–121 (1987).

    Article  CAS  PubMed  Google Scholar 

  27. Clafin, L. & Williams, K. Curr. Top. Mouse myeloma-spleen cell hybrids: enhanced hybridisation frequencies and rapid screening procedures. Microbiol. Immunol. 81, 107–109 (1978).

    Google Scholar 

  28. Micklem, L.R., McCann, M.C. & James, K. The use of rat mixed-thymocyte culutre-conditional medium for hybridoma production, cloning and revival. J. Immun. Meth. 104, 81–86 (1987).

    Article  CAS  Google Scholar 

  29. Yunis, J.J. & Sanchez, O. The G banded prophase chromosomes of man. Humangenetik 27, 167–172 (1975).

    CAS  PubMed  Google Scholar 

  30. Alhadeff, B., Velivasakis, M. & Siniscales, M. Cytogenet. Simultaneous identification of chromatid replication and of human chromosomes in metaphases of man-mouse somatic cell hybrids. Cell Genet. 19, 236–239 (1977).

    Article  CAS  Google Scholar 

  31. Maniatis, T., Fritsch, E.F. & Sambrook, J. Molecular Cloning: A Laboratory Manual. 3rd edn (Cold Spring Harbor Press, New York, 1989).

    Google Scholar 

  32. Bickmore, W.A., Maule, J.C., van Heyningen, V. & Porteous, D.P. Long-range structure of H-ras 1-selected transgenomes. Somat. Cell molec. Genet. 15, 229–235 (1989).

    Article  CAS  PubMed  Google Scholar 

  33. Link, A.J. & Maynard, O.V. Physical map of the Saccharomyces cerevisiae genome at 110-kilobase resolution. Genetics 127, 681–698 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

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Author notes

  1. Fiona M. Ross

    Present address: Wessex Regional Genetics Laboratory, Salisbury District Hospital, Odstock, Salisbury, SP2 8BJ, UK

Authors and Affiliations

  1. MRC Human Genetics Unit, Western General Hospital Crewe Road, Edinburgh, EH4 2XU, Scotland

    Alison G. Brown, Fiona M. Ross, Eimear M. Dunne, C. Michael Steel & Elizabeth M. Weir-Thompson

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Brown, A., Ross, F., Dunne, E. et al. Evidence for a new tumour suppressor locus (DBM) in human B–cell neoplasia telomeric to the retinoblastoma gene. Nat Genet 3, 67–72 (1993). https://doi.org/10.1038/ng0193-67

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