1887

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Volume 73, Issue 8

Human papillomavirus (HPV) type 16 and 33 E6/E7 region transcripts in tonsillar carcinomas can originate from integrated and episomal HPV DNA Free

Abstract

This study was undertaken to determine whether human papillomavirus (HPV) E6/E7 gene transcription in tonsillar carcinomas is correlated with viral DNA integration. Therefore, tonsillar carcinomas containing HPV-16 ( = 2) and HPV-33 ( = 2) DNA were analysed for the viral physical state and transcription of the E6/E7 region. Southern blot analysis, DNA polymerase chain reaction (PCR) and, eventually, two-dimensional gel electrophoresis revealed indications for the presence of only episomal DNA in the HPV-16-containing biopsies and only integrated DNA in one HPV-33-containing biopsy. The second HPV-33-containing carcinoma, from which one biopsy and two resected tumour specimens were analysed, showed a rather complex physical state profile. The biopsy of this tumour contained only episomal DNA, one resected tumour part contained only integrated DNA and the remaining tumour part contained both integrated and episomal HPV-33 DNA. Independent of the viral physical state, all biopsies and resected tumour parts tested showed the presence of E6/E7 transcripts as determined by RNA PCR. The results indicate that E6/E7 transcripts in tonsillar carcinomas can originate from integrated as well as episomal HPV DNA.

  • Received:
  • Accepted:
  • Published Online:
© Journal of General Virology 1992
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1992-08-01
2024-04-26
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References

  1. Awady M., Kaplan J., O’Brien S., Burk R. 1987; Molecular analysis of integrated papillomavirus 16 sequences in the cervical cancer cell line SiHa. Virology 159:389–398
     [Google Scholar]
  2. Baker C. C., Phelps W. C., Lindgren V., Braun M. J., Gonda M. A., Howley P. M. 1987; Structural and transcriptional analysis of human papillomavirus type 16 sequences in cervical carcinoma cell lines. Journal of Virology 61:962–972
     [Google Scholar]
  3. Barbosa M. S., Schlegel R. 1989; The E6 and E7 genes of HPV-18 are sufficient for inducing two-stage in vitro transformation of human keratinocytes. Oncogene 4:1529–1532
     [Google Scholar]
  4. Bernard B. A., Bailly C., Lenoir M. C., Darmon M., Thierry F., Yaniv M. 1989; The human papillomavirus type 18 (HPV 18) E2 gene product is a repressor of the HPV 18 regulatory region in human keratinocytes. Journal of Virology 63:4317–4324
     [Google Scholar]
  5. Broker T. R., Chow L. T., Chin M. T., Rhodes C. R., Wolinsky S. M., Whitbeck A., Stoler M. H. 1989; A molecular portrait of human papillomavirus carcinogenesis. Cancer Cells 7:197–208
     [Google Scholar]
  6. Choo K. B., Pau C. C., Hau S. H. 1987; Integration of human papillomavirus type 16 into cellular DNA of cervical carcinoma: preferential detection of the E2 gene and invariable retention of the long control region and the E6/E7 open reading frames. Virology 161:259–261
     [Google Scholar]
  7. Cole S. T., Streeck R. E. 1986; Genome organization and nucleotide sequence of human papillomavirus type 33, which is associated with cervical cancer. Journal of Virology 58:991–995
     [Google Scholar]
  8. Cripe T. P., Haugen T. H., Turk J. P., Tabatabai F., Schmid P. G., Dürst M., Gissmann L., Roman A., Turek L. P. 1987; Transcriptional regulation of the human papillomavirus-16 E6-E7 promoter by a keratinocyte-dependent enhancer, and by viral E2 trans-activator and repressor gene products: implications for cervical carcinogenesis. EMBO Journal 6:3745–3753
     [Google Scholar]
  9. Crook T., Morgenstern J. P., Crawford L., Banks L. 1989; Continued expression of HPV-16 E7 protein is required for maintenance of the transformed phenotype of cells cotransformed by HPV-16 plus EJ-ras. EMBO Journal 8:513–519
     [Google Scholar]
  10. Cullen A. P., Reid R., Campion M., Lörincz A. T. 1991; Analysis of the physical state of different human papillomavirus DNAs in intraepithelial and invasive cervical neoplasm. Journal of Virology 65:606–612
     [Google Scholar]
  11. Dürst M., Kleinheinz A., Hotz M., Gissmann L. 1985; The physical state of human papillomavirus type 16 DNA in benign and malignant genital tumours. Journal of General Virology 66:1515–1522
     [Google Scholar]
  12. Frohman M. A., Dush M. K., Martin G. R. 1988; Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. Proceedings of the National Academy of Sciences, U.S.A. 85:8998–9002
     [Google Scholar]
  13. Fuchs P., Girardi F., Pfister H. 1989; Human papillomavirus 16 DNA in cervical cancer patients: a diagnostic marker for early metastases?. International Journal of Cancer 43:41–44
     [Google Scholar]
  14. Gough N. M. 1988; Rapid and quantitative preparation of cytoplasmic RNA from small numbers of cells. Analytical Biochemistry 173:93–95
     [Google Scholar]
  15. Halbert C. L., Demers G. W., Galloway D. A. 1991; The E7 gene of human papillomavirus type 16 is sufficient for immortalization of human epithelial cells. Journal of Virology 65:473–478
     [Google Scholar]
  16. Hawley-Nelson P., Vousden K. H., Hubbert N. L., Lowy D. R., Schiller J. T. 1989; HPV 16 E6 and E7 proteins cooperate to immortalize primary human foreskin keratinocytes. EMBO Journal 8:3905–3910
     [Google Scholar]
  17. Inagaki Y., Tsunokawa Y., Takebe N., Nawa H., Nakanishi S., Terada M., Sugimura T. 1988; Nucleotide sequences of cDNAs for human papillomavirus type 18 transcripts in HeLa cells. Journal of Virology 62:1640–1646
     [Google Scholar]
  18. Lehn H., Villa L. L., Marziona F., Hilgarth M., Hillemans H. G., Sauer G. 1988; Physical state and biological activity of human papillomavirus genomes in precancerous lesions of the female genital tract. Journal of General Virology 69:187–196
     [Google Scholar]
  19. Matsukura T., Koi S., Sugase M. 1989; Both episomal and integrated forms of human papillomavirus type 16 are involved in invasive cervical cancers. Virology 172:63–72
     [Google Scholar]
  20. Münger K., Phelps W. C., Bubb V., Howley P. M., Schlegel R. 1989; The E6 and E7 genes of the human papillomavirus type 16 together are necessary and sufficient for transformation of primary human keratinocytes. Journal of Virology 63:4417–4421
     [Google Scholar]
  21. Nasseri M., Gage J. R., Lörincz A., Wettstein F. O. 1991; Human papillomavirus type 16 immortalized cervical keratinocytes contain transcripts encoding E6, E7, and E2 initiated at the P97 promoter and express high levels of E7. Virology 184:131–140
     [Google Scholar]
  22. Phelps W. C., Howley P. M. 1987; Transcriptional trans-activation by human papillomavirus type 16 E2 gene product. Journal of Virology 61:1630–1638
     [Google Scholar]
  23. Phelps W. C., Yee C. L., Münger K., Howley P. M. 1988; The human papillomavirus type 16 E7 gene encodes transactivation and transformation functions similar to those of adenovirus E1 A. Cell 53:539–547
     [Google Scholar]
  24. Riley J., Butter R., Ogilvie D., Finniear R., Jenner D., Powell S., Arnand R., Smith J. C., Markham A. F. 1990; A novel rapid method for the isolation of terminal sequences from yeast artificial chromosome (YAC) clones. Nucleic Acids Research 18:2887–2890
     [Google Scholar]
  25. Rohlfs M., Winkenbach S., Meyer S., Rupp T., Dürst M. 1991; Viral transcription in human keratinocyte cell lines immortalized by human papillomaviurs type-16. Virology 183:331–342
     [Google Scholar]
  26. Romanczuk H., Thierry F., Howley P. M. 1990; Mutational analysis of cis elements involved in E2 modulation of human papillomavirus type 16 P97 and type 18 PI05 promoters. Journal of Virology 64:2849–2859
     [Google Scholar]
  27. Schneider-Gädicke A., Schwarz E. 1986; Different human cervical carcinoma cell lines show similar transcription patterns of human papillomavirus type 18 early genes. EMBO Journal 5:2285–2292
     [Google Scholar]
  28. Schwarz E., Freese U. K., Gissmann L., Mayer W., Roggen-buck B., Stremlau A., zur Hausen H. 1985; Structure and transcription of human papillomavirus sequences in cervical carcinoma cells. Nature, London 314:111–114
     [Google Scholar]
  29. Seedorf K., Krämmer G., Dürst M., Suhai S., Röwekamp W. G. 1985; Human papillomavirus type 16 DNA sequence. Virology 145:181–185
     [Google Scholar]
  30. Shirasawa H., Tomita Y., Sekiya S., Takamizawa H., Simizu B. 1987; Integration and transcription of human papillomavirus type 16 and 18 sequences in cell lines derived from cervical carcinomas. Journal of General Virology 68:583–591
     [Google Scholar]
  31. Shirasawa H., Tomita Y., Kubota K., Kasai T., Sekiya S., Takamizawa H., Simizu B. 1988; Transcriptional differences of the human papillomavirus type 16 genome between precancerous lesions and invasive carcinomas. Journal of Virology 62:1022–1027
     [Google Scholar]
  32. Shirasawa H., Tomita Y., Fuse A., Yamamoto T., Tanzawa H., Sekiya S., Takamizawa H., Simizu B. 1989; Structure and expression of an integrated human papillomavirus type 16 genome amplified in a cervical carcinoma cell line. Journal of General Virology 70:1913–1919
     [Google Scholar]
  33. Smits H. L., Cornelissen M. T. E. Jebbink M. F., van den Tweel J. G., Struyk A. P. H. B., TerSchegget J. 1991; Human papillomavirus types 16 transcripts expressed from viral-cellular junctions and full-length viral copies in CaSki cells and in a cervical carcinoma. Virology 182:870–873
     [Google Scholar]
  34. Smotkin D., Wettstein F. O. 1986; Transcription of human papillomavirus type 16 early genes in a cervical cancer and a cancer-derived cell line and identification of the E7 protein. Proceedings of the National Academy of Sciences, U.S.A 83:4680–4684
     [Google Scholar]
  35. Smotkin D., Prokoph H., Wettstein F. O. 1989; Oncogenic and nononcogenic human genital papillomaviruses generate the E7 mRNA by different mechanisms. Journal of Virology 63:1441–1447
     [Google Scholar]
  36. Snijders P. J. F., Cromme F. V., van den Brule A. J. C., Schrijnemakers H. F. J., Snow G. B., Meijer C. J. L. M., Walboomers J. M. M. 1992a; Prevalence and expression of human papillomavirus in tonsillar carcinomas, indicating a possible viral etiology. International Journal of Cancer (in press)
    [Google Scholar]
  37. Snijders P. J. F., van den Brule A. J. C., Schrdnemakers H. F. J., Raaphorst P. M. C., Meijer C. J. L. M., Walboomers J. M. M. 1992b; Human papillomavirus type 33 in a tonsillar carcinoma generates its putative E7 mRNA via two E6* transcript species which are terminated at different early region poly(A) sites. Journal of Virology 66:3172–3178
     [Google Scholar]
  38. Storey A., Pim D., Murray A., Osborn K., Banks L., Crawford L. 1988; Comparison of the in vitro transforming activities of human papillomavirus types. EMBO Journal 7:1815–1820
     [Google Scholar]
  39. van den Brule A. J. C., Snijders P. J. F., Gordijn R. L. J., Bleker O. P., Meijer C. J. L. M., Walboomers J. M. M. 1990; General primer-mediated polymerase chain reaction permits the detection of sequenced and still unsequenced human papillomavirus genotypes in cervical scrapes and carcinomas. International Journal of Cancer 45:644–649
     [Google Scholar]
  40. van den Brule A. J. C., Cromme F. V., Snijders P. J. F., Smit L., Oudejans C. B. M., Baak J. P. A., Meijer C. J. L. M., Walboomers J. M. M. 1991; Non-radioactive RNA in situ hybridization detection of HPV 16-E7 transcripts in squamous cell carcinomas of the uterine cervix using confocal laser scan microscopy. American Journal of Pathology 139:1037–1045
     [Google Scholar]
  41. von Knebel Doeberitz M., Oltersdorf T., Schwarz E., Gissmann L. 1988; Correlation of modified human papillomavirus early gene expression with altered growth properties in C4-1 cervical carcinoma cells. Cancer Research 48:3780–3786
     [Google Scholar]
  42. Walboomers J. M. M., Melchers W. J. G., Mullink H., Meijer C. J. L. M., Struyk A., Quint W., van der Noordaa J., ter Schegget J. 1988; Sensitivity of in situ detection with biotinylated probes of human papilomavirus type 16 DNA in frozen tissue sections of squamous cell carcinomas of the cervix. American Journal of Pathology 131:587–594
     [Google Scholar]
  43. Wettstein F. O., Stevens J. G. 1982; Variable-sized free episomes of Shope papillomavirus DNA are present in all non-virus-producing neoplasms and integrated episomes are detected in some. Proceedings of the National Academy of Sciences, U.S.A 79:790–794
     [Google Scholar]
  44. Yee C., Krishnan-Hewlett I., Baker C. C., Schlegel R., Howley P. M. 1985; Presence and expression of human papillomavirus sequences in human cervical carcinoma cell lines. American Journal of Pathology 119:361–366
     [Google Scholar]
  45. Zur Hausen H. 1991; Human papillomaviruses in the pathogenesis of anogenital cancer. Virology 184:9–13
     [Google Scholar]
  46. Zur Hausen H., Schneider A. 1987; The role of papillomaviruses in anogenital cancer. In The Papillomaviruses pp. 245–263 Edited by Salzman N. P., Howley P. M. New York: Plenum Press;
     [Google Scholar]
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Human papillomavirus (HPV) type 16 and 33 E6/E7 region transcripts in tonsillar carcinomas can originate from integrated and episomal HPV DNA
J. Gen. Virol. 73, 2059 (1992); https://doi.org/10.1099/0022-1317-73-8-2059
/content/journal/jgv/10.1099/0022-1317-73-8-2059
/content/journal/jgv/10.1099/0022-1317-73-8-2059
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