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Microsatellite instability in primary neoplasms from HIV+ patients

Abstract

AIDS is associated with a high risk of certain malignancies, notably Kaposi's sarcoma (KS) and B-cell non-Hodgkin's lymphoma (NHL). The pathogenesis of these malignancies is not fully understood. One mechanism of malignant transformation recently described in colon tumorigenesis results from defects in DMA mismatch repair, manifest as widespread microsatellite instability. We demonstrate a high rate of microsatellite instability in KS and aggressive lymphomas obtained from HIV-infected patients, whereas there is no evidence of instability in similar lesions from HIV-negative patients. Further elucidation of the underlying mechanisms responsible for HIV-associated instability in primary tumours may provide insight into the pathogenesis of these AIDS-related neoplasms.

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References

  1. Reynolds, P., Saunders, L.D., Layefsky, M.E. & Lemp, G.F. The spectrum of acquired immuno-deficiency syndrome (AIDS)-associated malignancies in San Francisco, 1980–1987. Am.J.Epidemiol. 1, 19–30 (1993).

    Article  Google Scholar 

  2. Beral, V., Peterman, T.A., Berkelman, R.L. & Jaffe, H.W. Kaposi's sarcoma among persons with AIDS: a sexually transmitted infection? Lancet 335, 123–128 (1990).

    Article  CAS  Google Scholar 

  3. Knowles, D.M. Biologic aspects of AIDS-asspciated non-Hodgkin's lymphoma. Curr. Opin. Oncol. 5, 845–851 (1993).

    Article  CAS  Google Scholar 

  4. Beral, V., Peterman, T., Berkelman, R., Jaffe, H. AIDS-associated non-Hodgkin lymphoma. Lancet 337, 805–809 (1991).

    Article  CAS  Google Scholar 

  5. Centers for Disease Control. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR 41, 10–19 (1993).

  6. Peters, B.S. et al. Changing disease patterns in patients with AIDS in a referral centre in the United Kingdom: the changing face of AIDS. Br. med. J. 302, 203–207 (1991).

    Article  CAS  Google Scholar 

  7. Levine, A.M. Cancer in AIDS. Curr. Opin. Oncol. 5, 819–821 (1993).

    Article  CAS  Google Scholar 

  8. Shibata, D. et al. Epstein-Barr virus-associated non-Hodgkin's lymphoma in patients infected with the human immunodeficiency virus. Blood 8, 2102–2109 (1993).

    Google Scholar 

  9. Aaltonen, L.A. et al. Clues to the pathogenesis of familial colorectal cancer. Science 260, 812–816 (1993).

    Article  CAS  Google Scholar 

  10. Thibodeau, S.N., Li, G. & Schaid, D. Microsatellite instability in cancer of the proximal colon. Science 260, 816–819 (1993).

    Article  CAS  Google Scholar 

  11. Ionov, Y., Peinado, M.A., Malkhosyan, S., Shibata, D. & Perucho, M. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanisms for colonic carcinogenesis. Nature 363, 558–561 (1993).

    Article  CAS  Google Scholar 

  12. Modrich, P. Mechanisms and biological effects of mismatch repair. Annu. Rev. Genet. 25, 229–253 (1991).

    Article  CAS  Google Scholar 

  13. Strand, M., Prolla, T.A., Liskay, R.M. & Petes, T.D. Destabilization of tracts of simple repetetive DNA in yeast by mutations affecting DNA mismatch repair. Nature 365, 274–276 (1993).

    Article  CAS  Google Scholar 

  14. Fishel, R. et al. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell 75, 1027–1038 (1993).

    Article  CAS  Google Scholar 

  15. Leach, F.S. et al. Mutations of a mutS homolog in hereditary non polyposis colorectal cancer. Cell 75, 1215–1225 (1993).

    Article  CAS  Google Scholar 

  16. Papadopoulos, N. et al. Mutation of a mutL homolog in hereditary colon cancer. Science 263, 1625–1629 (1994).

    Article  CAS  Google Scholar 

  17. Bronner, C.E. et al. Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature 368, 258–261 (1994).

    Article  CAS  Google Scholar 

  18. Nicolaides, N.C. et al. Mutations of two PMS homologues in hereditary nonpolyposis colon cancer. Nature 371, 75–80 (1994).

    Article  CAS  Google Scholar 

  19. Lipsey, L.R. & Northfelt, D.W. Anogenital neoplasia in patients with HIV infection. Curr. Opin. Oncol 5, 861–866 (1993).

    Article  CAS  Google Scholar 

  20. Farzadegan, H. et al. Detection of human immunodeficiency virus type 1 infection by polymerase chain reaction in a cohort of seronegative intravenous drug users. J. infect. Dis. 168, 327–331 (1993).

    Article  CAS  Google Scholar 

  21. Parsons, R. et al. Hypermutability and mismatch repair deficiency in RER+ tumour cells. Cell 75, 1227–1236 (1993).

    Article  CAS  Google Scholar 

  22. Wooster, R. et al. Instability of short tandem repeats (microsatellites) in human cancers. Nature Genet. 6, 152–156 (1994).

    Article  CAS  Google Scholar 

  23. Mao, L. et al. Microsatellite alterations as clonal markers for the detection of human cancer. Proc. natn. Acad. Sci U.S.A. 91, 987l9875 (1994).

    Article  CAS  Google Scholar 

  24. Merlo, A. et al. Frequent microsatellite instability in primary small cell lung cancer. Cancer Res. 54, 2098–2101 (1994).

    CAS  Google Scholar 

  25. Glebov, O.K., McKenzie, K.E., White, C.A. & Sukumar, S. Frequent p53 mutations and novel alleles in familial breast cancer. Cancer Res. 54, 3703–3709 (1994).

    CAS  Google Scholar 

  26. Ensoli, B., Barillari, G., Salahuddin, S.Z., Gallo, R.C. & Wong-Staal, F. Tat protein of HIV–1 stimulates growth of cells derived from Kaposi's sarcoma lesions of AIDS patients. Nature 345, 84–86 (1990).

    Article  CAS  Google Scholar 

  27. Vogel, J., Hinrichs, S.H., Reynolds, R.K., Luciw, P.A. & Jay, G. The HIV tat gene induces dermal lesions resembling Kaposi's sarcoma in transgenic mice. Nature 335, 606–611 (1988).

    Article  CAS  Google Scholar 

  28. Bovi, P.D. et al. Presence of chromosomal abnormalities and lack of AIDS retrovirus DNA sequences in AIDS-associated Kaposi's sarcoma. Cancer Res. 46, 6333–6338 (1986).

    Google Scholar 

  29. Pelicci, P. et al. Multiple monoclonal B cell expansions and c-myc oncogene rearrangements in acquired immune deficiency syndrome-related lymphopro-liferative disorders. J. exp. Med. 164, 2049–2060 (1986).

    Article  CAS  Google Scholar 

  30. Groopman, J.E. et al. Pathogenesis of B cell lymphoma in a patient with AIDS. Blood 67, 612–615 (1986).

    CAS  PubMed  Google Scholar 

  31. Astrin, S.M., Schattner, E., Laurence, J., Lebman, R.I. & Rodriguez-Alfageme, C. Does HIV infection of B lymphocytes initiate AIDS lymphoma? Detection by PCR of viral sequences in lymphoma tissue. Curr. Top. Microbiol Immunol 182, 399–407 (1992).

    CAS  PubMed  Google Scholar 

  32. Galloway, D.A. & McDougall, J.K. The oncogenic potential of herpes simplex viruses: evidence for a ‘hit-and-run’ mechanism. Nature 302, 21–24 (1983).

    Article  CAS  Google Scholar 

  33. Radman, M. & Wagner, R., Carcinogenesis: Missing mismatch repair. Nature 366, 722 (1993).

    Article  CAS  Google Scholar 

  34. Thompson, J. et al. A transforming fragment within the direct repeat region of human herpesvirus type 6 that transactivates HIV–. Oncogene 9, 1167–1175 (1994).

    CAS  PubMed  Google Scholar 

  35. van der Riet, P. et al. Progression of basal cell carcinoma through loss of chromosome 9q and inactivation of a single p53 allele. Cancer Res. 54, 25–27 (1994).

    CAS  PubMed  Google Scholar 

  36. Coutlée, F., Viscidi, R.P., Saint-Antoine, P., Kessous, A. & Yolken, R.H. The polymerase chain reaction: a new tool for the understanding and diagnosis of HIV–1 infection at the molecular level. Mol. Cell. Probes 5, 241–259 (1991).

    Article  Google Scholar 

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Bedi, G., Westra, W., Farzadegan, H. et al. Microsatellite instability in primary neoplasms from HIV+ patients. Nat Med 1, 65–68 (1995). https://doi.org/10.1038/nm0195-65

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