Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1994 Mar;68(3):1309–1315. doi: 10.1128/jvi.68.3.1309-1315.1994

Alterations of the p53 gene in Epstein-Barr virus-associated immunodeficiency-related lymphomas.

R H Edwards 1, N Raab-Traub 1
PMCID: PMC236584  PMID: 8107196

Abstract

Mutations of the p53 tumor suppressor gene are among the most common genetic alterations found in many different human malignancies, including those of the colon, lung, and breast. Alterations in wild-type p53 lead to loss of the suppressor function and thus contribute to tumorigenesis. The potential role of p53 mutations in a sampling of B-cell lymphomas, the majority of which were associated with Epstein-Barr virus (EBV), was investigated. Twenty-six biopsy specimens from immunocompromised patients, including allograft recipients and patients with AIDS, Wiscott-Aldrich syndrome, and human T-cell leukemia virus type 1 infection, in comparison with three Burkitt lymphomas and four Burkitt lymphoma cell lines were analyzed. Mutation in p53 was detected in all four Burkitt lymphoma cell lines as well as the three Burkitt lymphoma biopsy specimens. In patients with AIDS, 5 of 10 lymphomas were EBV positive, and 1 had a mutation in p53. Mutation in p53 was not detected in 14 EBV-positive lymphomas which arose in transplant recipients. These data indicate that with the exception of Burkitt lymphomas, p53 mutations are not involved in the majority EBV-positive B-cell lymphomas which develop in immunocompromised patients.

Full text

PDF
1309

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baker S. J., Markowitz S., Fearon E. R., Willson J. K., Vogelstein B. Suppression of human colorectal carcinoma cell growth by wild-type p53. Science. 1990 Aug 24;249(4971):912–915. doi: 10.1126/science.2144057. [DOI] [PubMed] [Google Scholar]
  2. Ballerini P., Gaidano G., Gong J., Tassi V., Saglio G., Knowles D. M., Dalla-Favera R. Molecular pathogenesis of HIV-associated lymphomas. AIDS Res Hum Retroviruses. 1992 May;8(5):731–735. [PubMed] [Google Scholar]
  3. Bhatia K. G., Gutiérrez M. I., Huppi K., Siwarski D., Magrath I. T. The pattern of p53 mutations in Burkitt's lymphoma differs from that of solid tumors. Cancer Res. 1992 Aug 1;52(15):4273–4276. [PubMed] [Google Scholar]
  4. Bhatia K., Gutiérrez M. I., Huppi K., Magrath I. T. PCR detection of a neutral CGA/CGG dimorphism in exon 6 of the human p53 gene. Nucleic Acids Res. 1992 Feb 25;20(4):928–928. doi: 10.1093/nar/20.4.928-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Buchman V. L., Chumakov P. M., Ninkina N. N., Samarina O. P., Georgiev G. P. A variation in the structure of the protein-coding region of the human p53 gene. Gene. 1988 Oct 30;70(2):245–252. doi: 10.1016/0378-1119(88)90196-5. [DOI] [PubMed] [Google Scholar]
  6. Cawthon R. M., Weiss R., Xu G. F., Viskochil D., Culver M., Stevens J., Robertson M., Dunn D., Gesteland R., O'Connell P. A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations. Cell. 1990 Jul 13;62(1):193–201. doi: 10.1016/0092-8674(90)90253-b. [DOI] [PubMed] [Google Scholar]
  7. Chappuis B. B., Müller H., Stutte J., Hey M. M., Hübner K., Müller-Hermelink H. K. Identification of EBV-DNA in lymph nodes from patients with lymphadenopathy and lymphomas associated with AIDS. Virchows Arch B Cell Pathol Incl Mol Pathol. 1990;58(3):199–205. doi: 10.1007/BF02890072. [DOI] [PubMed] [Google Scholar]
  8. Dalla-Favera R., Bregni M., Erikson J., Patterson D., Gallo R. C., Croce C. M. Human c-myc onc gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7824–7827. doi: 10.1073/pnas.79.24.7824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Desgranges C., Wolf H., De-Thé G., Shanmugaratnam K., Cammoun N., Ellouz R., Klein G., Lennert K., Muñoz N., Zur Hausen H. Nasopharyngeal carcinoma. X. Presence of epstein-barr genomes in separated epithelial cells of tumours in patients from Singapore, Tunisia and Kenya. Int J Cancer. 1975 Jul 15;16(1):7–15. doi: 10.1002/ijc.2910160103. [DOI] [PubMed] [Google Scholar]
  10. Duthu A., Debuire B., Romano J., Ehrhart J. C., Fiscella M., May E., Appella E., May P. p53 mutations in Raji cells: characterization and localization relative to other Burkitt's lymphomas. Oncogene. 1992 Nov;7(11):2161–2167. [PubMed] [Google Scholar]
  11. Effert P. J., McCoy R. H., Walther P. J., Liu E. T. p53 gene alterations in human prostate carcinoma. J Urol. 1993 Jul;150(1):257–261. doi: 10.1016/s0022-5347(17)35458-7. [DOI] [PubMed] [Google Scholar]
  12. Effert P. J., Neubauer A., Walther P. J., Liu E. T. Alterations of the P53 gene are associated with the progression of a human prostate carcinoma. J Urol. 1992 Mar;147(3 Pt 2):789–793. doi: 10.1016/s0022-5347(17)37387-1. [DOI] [PubMed] [Google Scholar]
  13. Effert P., McCoy R., Abdel-Hamid M., Flynn K., Zhang Q., Busson P., Tursz T., Liu E., Raab-Traub N. Alterations of the p53 gene in nasopharyngeal carcinoma. J Virol. 1992 Jun;66(6):3768–3775. doi: 10.1128/jvi.66.6.3768-3775.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Eliyahu D., Michalovitz D., Eliyahu S., Pinhasi-Kimhi O., Oren M. Wild-type p53 can inhibit oncogene-mediated focus formation. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8763–8767. doi: 10.1073/pnas.86.22.8763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Farrell P. J., Allan G. J., Shanahan F., Vousden K. H., Crook T. p53 is frequently mutated in Burkitt's lymphoma cell lines. EMBO J. 1991 Oct;10(10):2879–2887. doi: 10.1002/j.1460-2075.1991.tb07837.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Finlay C. A., Hinds P. W., Levine A. J. The p53 proto-oncogene can act as a suppressor of transformation. Cell. 1989 Jun 30;57(7):1083–1093. doi: 10.1016/0092-8674(89)90045-7. [DOI] [PubMed] [Google Scholar]
  17. Fåhraeus R., Fu H. L., Ernberg I., Finke J., Rowe M., Klein G., Falk K., Nilsson E., Yadav M., Busson P. Expression of Epstein-Barr virus-encoded proteins in nasopharyngeal carcinoma. Int J Cancer. 1988 Sep 15;42(3):329–338. doi: 10.1002/ijc.2910420305. [DOI] [PubMed] [Google Scholar]
  18. Gaidano G., Ballerini P., Gong J. Z., Inghirami G., Neri A., Newcomb E. W., Magrath I. T., Knowles D. M., Dalla-Favera R. p53 mutations in human lymphoid malignancies: association with Burkitt lymphoma and chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5413–5417. doi: 10.1073/pnas.88.12.5413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Geser A., Lenoir G. M., Anvret M., Bornkamm G., Klein G., Williams E. H., Wright D. H., De-The G. Epstein-Barr virus markers in a series of Burkitt's lymphomas from the West Nile District, Uganda. Eur J Cancer Clin Oncol. 1983 Oct;19(10):1393–1404. doi: 10.1016/0277-5379(93)90009-t. [DOI] [PubMed] [Google Scholar]
  20. Gilligan K., Sato H., Rajadurai P., Busson P., Young L., Rickinson A., Tursz T., Raab-Traub N. Novel transcription from the Epstein-Barr virus terminal EcoRI fragment, DIJhet, in a nasopharyngeal carcinoma. J Virol. 1990 Oct;64(10):4948–4956. doi: 10.1128/jvi.64.10.4948-4956.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Gratama J. W., Zutter M. M., Minarovits J., Oosterveer M. A., Thomas E. D., Klein G., Ernberg I. Expression of Epstein-Barr virus-encoded growth-transformation-associated proteins in lymphoproliferations of bone-marrow transplant recipients. Int J Cancer. 1991 Jan 21;47(2):188–192. doi: 10.1002/ijc.2910470205. [DOI] [PubMed] [Google Scholar]
  22. Gregory C. D., Dive C., Henderson S., Smith C. A., Williams G. T., Gordon J., Rickinson A. B. Activation of Epstein-Barr virus latent genes protects human B cells from death by apoptosis. Nature. 1991 Feb 14;349(6310):612–614. doi: 10.1038/349612a0. [DOI] [PubMed] [Google Scholar]
  23. Gulley M. L., Raphael M., Lutz C. T., Ross D. W., Raab-Traub N. Epstein-Barr virus integration in human lymphomas and lymphoid cell lines. Cancer. 1992 Jul 1;70(1):185–191. doi: 10.1002/1097-0142(19920701)70:1<185::aid-cncr2820700129>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
  24. Hanto D. W., Frizzera G., Gajl-Peczalska K. J., Sakamoto K., Purtilo D. T., Balfour H. H., Jr, Simmons R. L., Najarian J. S. Epstein-Barr virus-induced B-cell lymphoma after renal transplantation: acyclovir therapy and transition from polyclonal to monoclonal B-cell proliferation. N Engl J Med. 1982 Apr 15;306(15):913–918. doi: 10.1056/NEJM198204153061506. [DOI] [PubMed] [Google Scholar]
  25. Hinuma Y., Grace J. T., Jr Cloning of immunoglobulin-producing human leukemic and lymphoma cells in long-term cultures. Proc Soc Exp Biol Med. 1967 Jan;124(1):107–111. doi: 10.3181/00379727-124-31677. [DOI] [PubMed] [Google Scholar]
  26. Hitt M. M., Allday M. J., Hara T., Karran L., Jones M. D., Busson P., Tursz T., Ernberg I., Griffin B. E. EBV gene expression in an NPC-related tumour. EMBO J. 1989 Sep;8(9):2639–2651. doi: 10.1002/j.1460-2075.1989.tb08404.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Hollstein M., Sidransky D., Vogelstein B., Harris C. C. p53 mutations in human cancers. Science. 1991 Jul 5;253(5015):49–53. doi: 10.1126/science.1905840. [DOI] [PubMed] [Google Scholar]
  28. Horn G. T., Richards B., Klinger K. W. Amplification of a highly polymorphic VNTR segment by the polymerase chain reaction. Nucleic Acids Res. 1989 Mar 11;17(5):2140–2140. doi: 10.1093/nar/17.5.2140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ichikawa A., Hotta T., Takagi N., Tsushita K., Kinoshita T., Nagai H., Murakami Y., Hayashi K., Saito H. Mutations of p53 gene and their relation to disease progression in B-cell lymphoma. Blood. 1992 May 15;79(10):2701–2707. [PubMed] [Google Scholar]
  30. Katz B. Z., Raab-Traub N., Miller G. Latent and replicating forms of Epstein-Barr virus DNA in lymphomas and lymphoproliferative diseases. J Infect Dis. 1989 Oct;160(4):589–598. doi: 10.1093/infdis/160.4.589. [DOI] [PubMed] [Google Scholar]
  31. Klein G., Dombos L. Relationship between the sensitivity of EBV-carrying lymphoblastoid lines to superinfection and the inducibility of the resident viral genome. Int J Cancer. 1973 Mar 15;11(2):327–337. doi: 10.1002/ijc.2910110210. [DOI] [PubMed] [Google Scholar]
  32. Lane D. P., Crawford L. V. T antigen is bound to a host protein in SV40-transformed cells. Nature. 1979 Mar 15;278(5701):261–263. doi: 10.1038/278261a0. [DOI] [PubMed] [Google Scholar]
  33. Lavigueur A., Maltby V., Mock D., Rossant J., Pawson T., Bernstein A. High incidence of lung, bone, and lymphoid tumors in transgenic mice overexpressing mutant alleles of the p53 oncogene. Mol Cell Biol. 1989 Sep;9(9):3982–3991. doi: 10.1128/mcb.9.9.3982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Linzer D. I., Levine A. J. Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells. Cell. 1979 May;17(1):43–52. doi: 10.1016/0092-8674(79)90293-9. [DOI] [PubMed] [Google Scholar]
  35. MacMahon E. M., Glass J. D., Hayward S. D., Mann R. B., Becker P. S., Charache P., McArthur J. C., Ambinder R. F. Epstein-Barr virus in AIDS-related primary central nervous system lymphoma. Lancet. 1991 Oct 19;338(8773):969–973. doi: 10.1016/0140-6736(91)91837-k. [DOI] [PubMed] [Google Scholar]
  36. Neubauer A., Neubauer B., Liu E. Polymerase chain reaction based assay to detect allelic loss in human DNA: loss of beta-interferon gene in chronic myelogenous leukemia. Nucleic Acids Res. 1990 Feb 25;18(4):993–998. doi: 10.1093/nar/18.4.993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Nigro J. M., Baker S. J., Preisinger A. C., Jessup J. M., Hostetter R., Cleary K., Bigner S. H., Davidson N., Baylin S., Devilee P. Mutations in the p53 gene occur in diverse human tumour types. Nature. 1989 Dec 7;342(6250):705–708. doi: 10.1038/342705a0. [DOI] [PubMed] [Google Scholar]
  38. Orita M., Suzuki Y., Sekiya T., Hayashi K. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics. 1989 Nov;5(4):874–879. doi: 10.1016/0888-7543(89)90129-8. [DOI] [PubMed] [Google Scholar]
  39. PULVERTAFT J. V. A STUDY OF MALIGNANT TUMOURS IN NIGERIA BY SHORT-TERM TISSUE CULTURE. J Clin Pathol. 1965 May;18:261–273. doi: 10.1136/jcp.18.3.261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Raab-Traub N., Dambaugh T., Kieff E. DNA of Epstein-Barr virus VIII: B95-8, the previous prototype, is an unusual deletion derivative. Cell. 1980 Nov;22(1 Pt 1):257–267. doi: 10.1016/0092-8674(80)90173-7. [DOI] [PubMed] [Google Scholar]
  41. Raab-Traub N., Flynn K., Pearson G., Huang A., Levine P., Lanier A., Pagano J. The differentiated form of nasopharyngeal carcinoma contains Epstein-Barr virus DNA. Int J Cancer. 1987 Jan 15;39(1):25–29. doi: 10.1002/ijc.2910390106. [DOI] [PubMed] [Google Scholar]
  42. Rowe M., Rowe D. T., Gregory C. D., Young L. S., Farrell P. J., Rupani H., Rickinson A. B. Differences in B cell growth phenotype reflect novel patterns of Epstein-Barr virus latent gene expression in Burkitt's lymphoma cells. EMBO J. 1987 Sep;6(9):2743–2751. doi: 10.1002/j.1460-2075.1987.tb02568.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Scheffner M., Werness B. A., Huibregtse J. M., Levine A. J., Howley P. M. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell. 1990 Dec 21;63(6):1129–1136. doi: 10.1016/0092-8674(90)90409-8. [DOI] [PubMed] [Google Scholar]
  44. Sidransky D., Von Eschenbach A., Tsai Y. C., Jones P., Summerhayes I., Marshall F., Paul M., Green P., Hamilton S. R., Frost P. Identification of p53 gene mutations in bladder cancers and urine samples. Science. 1991 May 3;252(5006):706–709. doi: 10.1126/science.2024123. [DOI] [PubMed] [Google Scholar]
  45. Takahashi T., Nau M. M., Chiba I., Birrer M. J., Rosenberg R. K., Vinocour M., Levitt M., Pass H., Gazdar A. F., Minna J. D. p53: a frequent target for genetic abnormalities in lung cancer. Science. 1989 Oct 27;246(4929):491–494. doi: 10.1126/science.2554494. [DOI] [PubMed] [Google Scholar]
  46. Thomas J. A., Hotchin N. A., Allday M. J., Amlot P., Rose M., Yacoub M., Crawford D. H. Immunohistology of Epstein-Barr virus-associated antigens in B cell disorders from immunocompromised individuals. Transplantation. 1990 May;49(5):944–953. doi: 10.1097/00007890-199005000-00022. [DOI] [PubMed] [Google Scholar]
  47. Toguchida J., Yamaguchi T., Ritchie B., Beauchamp R. L., Dayton S. H., Herrera G. E., Yamamuro T., Kotoura Y., Sasaki M. S., Little J. B. Mutation spectrum of the p53 gene in bone and soft tissue sarcomas. Cancer Res. 1992 Nov 15;52(22):6194–6199. [PubMed] [Google Scholar]
  48. Young L. S., Dawson C. W., Clark D., Rupani H., Busson P., Tursz T., Johnson A., Rickinson A. B. Epstein-Barr virus gene expression in nasopharyngeal carcinoma. J Gen Virol. 1988 May;69(Pt 5):1051–1065. doi: 10.1099/0022-1317-69-5-1051. [DOI] [PubMed] [Google Scholar]
  49. Young L., Alfieri C., Hennessy K., Evans H., O'Hara C., Anderson K. C., Ritz J., Shapiro R. S., Rickinson A., Kieff E. Expression of Epstein-Barr virus transformation-associated genes in tissues of patients with EBV lymphoproliferative disease. N Engl J Med. 1989 Oct 19;321(16):1080–1085. doi: 10.1056/NEJM198910193211604. [DOI] [PubMed] [Google Scholar]
  50. van Santen V., Cheung A., Kieff E. Epstein-Barr virus RNA VII: size and direction of transcription of virus-specified cytoplasmic RNAs in a transformed cell line. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1930–1934. doi: 10.1073/pnas.78.3.1930. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. zur Hausen H., Schulte-Holthausen H., Klein G., Henle W., Henle G., Clifford P., Santesson L. EBV DNA in biopsies of Burkitt tumours and anaplastic carcinomas of the nasopharynx. Nature. 1970 Dec 12;228(5276):1056–1058. doi: 10.1038/2281056a0. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES