Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 Jul 19;91(15):6953–6957. doi: 10.1073/pnas.91.15.6953

Loss of heterozygosity in cervical carcinoma: subchromosomal localization of a putative tumor-suppressor gene to chromosome 11q22-q24.

G M Hampton 1, L A Penny 1, R N Baergen 1, A Larson 1, C Brewer 1, S Liao 1, R M Busby-Earle 1, A W Williams 1, C M Steel 1, C C Bird 1, et al.
PMCID: PMC44316  PMID: 8041728

Abstract

Infection of cervical epithelial cells with so-called "aggressive" subtypes of human papilloma virus (HPV) appears to be an important factor in the etiology of cervical carcinoma. However, mounting evidence suggests that additional genetic changes are required for progression to an invasive carcinoma. Functional studies have shown that human chromosome 11 contains a gene or genes capable of suppressing tumorigenicity in cell lines derived from different histopathological types of cervical carcinoma, suggesting that aberration of this gene(s) may represent at least one of the additional changes required for tumorigenic progression. To identify the likely chromosomal position of this gene(s), we have carried out a systematic genetic analysis of chromosome 11 in the primary tumors of 32 patients with cervical carcinoma. Sixteen highly polymorphic markers, 10 of which were based on simple sequence repeats typed by PCR, were used to compare matched DNA samples from noninvolved tissue and portions of tumor tissue highly enriched for neoplastic cells by the cryostat-sectioning technique. Of the 32 patients examined, 14 (44%) demonstrated clonal genetic alterations resulting in loss of heterozygosity for one or more markers. Seven of the clonal genetic alterations on chromosome 11 were specific to the long arm, and the overlap between these and other allelic deletions suggests that a suppressor gene(s) relevant to cervical carcinoma maps to chromosome 11q22-q24.

Full text

PDF
6953

Images in this article

6955Image
on p.6955
6956Image
on p.6956

Selected References

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

  1. Bhattacharya S., Wilson T. M., Wojciechowski A. P., Volpe C. P., Scott J. Hypervariable polymorphism in the APOC3 gene. Nucleic Acids Res. 1991 Sep 11;19(17):4799–4799. doi: 10.1093/nar/19.17.4799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brookes S., Smith R., Casey G., Dickson C., Peters G. Sequence organization of the human int-2 gene and its expression in teratocarcinoma cells. Oncogene. 1989 Apr;4(4):429–436. [PubMed] [Google Scholar]
  3. Busby-Earle R. M., Steel C. M., Bird C. C. Cervical carcinoma: low frequency of allele loss at loci implicated in other common malignancies. Br J Cancer. 1993 Jan;67(1):71–75. doi: 10.1038/bjc.1993.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cavenee W. K., Dryja T. P., Phillips R. A., Benedict W. F., Godbout R., Gallie B. L., Murphree A. L., Strong L. C., White R. L. Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. 1983 Oct 27-Nov 2Nature. 305(5937):779–784. doi: 10.1038/305779a0. [DOI] [PubMed] [Google Scholar]
  5. Cawkwell L., Bell S. M., Lewis F. A., Dixon M. F., Taylor G. R., Quirke P. Rapid detection of allele loss in colorectal tumours using microsatellites and fluorescent DNA technology. Br J Cancer. 1993 Jun;67(6):1262–1267. doi: 10.1038/bjc.1993.236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Eubanks J. H., Selleri L., Hart R., Rosette C., Evans G. A. Isolation, localization, and physical mapping of a highly polymorphic locus on human chromosome 11q13. Genomics. 1991 Nov;11(3):720–729. doi: 10.1016/0888-7543(91)90080-x. [DOI] [PubMed] [Google Scholar]
  7. Fearon E. R., Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990 Jun 1;61(5):759–767. doi: 10.1016/0092-8674(90)90186-i. [DOI] [PubMed] [Google Scholar]
  8. Foulkes W. D., Campbell I. G., Stamp G. W., Trowsdale J. Loss of heterozygosity and amplification on chromosome 11q in human ovarian cancer. Br J Cancer. 1993 Feb;67(2):268–273. doi: 10.1038/bjc.1993.51. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gessler M., König A., Bruns G. A. The genomic organization and expression of the WT1 gene. Genomics. 1992 Apr;12(4):807–813. doi: 10.1016/0888-7543(92)90313-h. [DOI] [PubMed] [Google Scholar]
  10. Goelz S. E., Hamilton S. R., Vogelstein B. Purification of DNA from formaldehyde fixed and paraffin embedded human tissue. Biochem Biophys Res Commun. 1985 Jul 16;130(1):118–126. doi: 10.1016/0006-291x(85)90390-0. [DOI] [PubMed] [Google Scholar]
  11. Goodrich D. W., Lee W. H. The molecular genetics of retinoblastoma. Cancer Surv. 1990;9(3):529–554. [PubMed] [Google Scholar]
  12. Hampton G. M., Howe C., Leuteritz G., Thomas H., Bodmer W. F., Solomon E., Ballhausen W. G. Regional mapping of 22 microclones around the adenomatous polyposis coli (APC) locus on chromosome 5q. Hum Genet. 1991 Nov;88(1):112–114. doi: 10.1007/BF00204940. [DOI] [PubMed] [Google Scholar]
  13. Iwasaki H., Stewart P. W., Dilley W. G., Holt M. S., Steinbrueck T. D., Wells S. A., Jr, Donis-Keller H. A minisatellite and a microsatellite polymorphism within 1.5 kb at the human muscle glycogen phosphorylase (PYGM) locus can be amplified by PCR and have combined informativeness of PIC 0.95. Genomics. 1992 May;13(1):7–15. doi: 10.1016/0888-7543(92)90194-w. [DOI] [PubMed] [Google Scholar]
  14. Jones M. H., Nakamura Y. Deletion mapping of chromosome 3p in female genital tract malignancies using microsatellite polymorphisms. Oncogene. 1992 Aug;7(8):1631–1634. [PubMed] [Google Scholar]
  15. Keldysh P. L., Dragani T. A., Fleischman E. W., Konstantinova L. N., Perevoschikov A. G., Pierotti M. A., Della Porta G., Kopnin B. P. 11q deletions in human colorectal carcinomas: cytogenetics and restriction fragment length polymorphism analysis. Genes Chromosomes Cancer. 1993 Jan;6(1):45–50. doi: 10.1002/gcc.2870060109. [DOI] [PubMed] [Google Scholar]
  16. Knudson A. G., Jr Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A. 1971 Apr;68(4):820–823. doi: 10.1073/pnas.68.4.820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Larsen P. M., Vetner M., Hansen K., Fey S. J. Future trends in cervical cancer. Cancer Lett. 1988 Aug 15;41(2):123–137. doi: 10.1016/0304-3835(88)90109-7. [DOI] [PubMed] [Google Scholar]
  18. Lasko D., Cavenee W., Nordenskjöld M. Loss of constitutional heterozygosity in human cancer. Annu Rev Genet. 1991;25:281–314. doi: 10.1146/annurev.ge.25.120191.001433. [DOI] [PubMed] [Google Scholar]
  19. Litt M., Eubanks J. H., Evans G. A., Phromchotikul T. Regional localization of the highly polymorphic locus D11S533 on the linkage map of human chromosome 11q. Genomics. 1992 Nov;14(3):820–820. doi: 10.1016/s0888-7543(05)80199-5. [DOI] [PubMed] [Google Scholar]
  20. Litt M., Hauge X., Sharma V. Shadow bands seen when typing polymorphic dinucleotide repeats: some causes and cures. Biotechniques. 1993 Aug;15(2):280–284. [PubMed] [Google Scholar]
  21. Litt M., Kramer P., Hauge X. Y., Weber J. L., Wang Z., Wilkie P. J., Holt M. S., Mishra S., Donis-Keller H., Warnich L. A microsatellite-based index map of human chromosome 11. Hum Mol Genet. 1993 Jul;2(7):909–913. doi: 10.1093/hmg/2.7.909. [DOI] [PubMed] [Google Scholar]
  22. Litt M., Sharma V., Luty J. A. Dinucleotide repeat polymorphism at the D11S35 locus. Nucleic Acids Res. 1990 Oct 11;18(19):5921–5921. doi: 10.1093/nar/18.19.5921-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Misra B. C., Srivatsan E. S. Localization of HeLa cell tumor-suppressor gene to the long arm of chromosome II. Am J Hum Genet. 1989 Oct;45(4):565–577. [PMC free article] [PubMed] [Google Scholar]
  24. Oshimura M., Kugoh H., Koi M., Shimizu M., Yamada H., Satoh H., Barrett J. C. Transfer of a normal human chromosome 11 suppresses tumorigenicity of some but not all tumor cell lines. J Cell Biochem. 1990 Mar;42(3):135–142. doi: 10.1002/jcb.240420304. [DOI] [PubMed] [Google Scholar]
  25. Polymeropoulos M. H., Xiao H., Rath D. S., Merril C. R. Dinucleotide repeat polymorphism at the human non-histone chromosomal protein HMG14 gene. Nucleic Acids Res. 1991 Jul 11;19(13):3753–3753. [PMC free article] [PubMed] [Google Scholar]
  26. Saxon P. J., Srivatsan E. S., Stanbridge E. J. Introduction of human chromosome 11 via microcell transfer controls tumorigenic expression of HeLa cells. EMBO J. 1986 Dec 20;5(13):3461–3466. doi: 10.1002/j.1460-2075.1986.tb04670.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sealey P. G., Whittaker P. A., Southern E. M. Removal of repeated sequences from hybridisation probes. Nucleic Acids Res. 1985 Mar 25;13(6):1905–1922. doi: 10.1093/nar/13.6.1905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Smith M. W., Clark S. P., Hutchinson J. S., Wei Y. H., Churukian A. C., Daniels L. B., Diggle K. L., Gen M. W., Romo A. J., Lin Y. A sequence-tagged site map of human chromosome 11. Genomics. 1993 Sep;17(3):699–725. doi: 10.1006/geno.1993.1392. [DOI] [PubMed] [Google Scholar]
  29. Srivatsan E. S., Misra B. C., Venugopalan M., Wilczynski S. P. Loss of heterozygosity for alleles on chromosome II in cervical carcinoma. Am J Hum Genet. 1991 Oct;49(4):868–877. [PMC free article] [PubMed] [Google Scholar]
  30. Tokino T., Takahashi E., Mori M., Tanigami A., Glaser T., Park J. W., Jones C., Hori T., Nakamura Y. Isolation and mapping of 62 new RFLP markers on human chromosome 11. Am J Hum Genet. 1991 Feb;48(2):258–268. [PMC free article] [PubMed] [Google Scholar]
  31. Tomlinson I. P., Gammack A. J., Stickland J. E., Mann G. J., MacKie R. M., Kefford R. F., McGee J. O. Loss of heterozygosity in malignant melanoma at loci on chromosome 11 and 17 implicated in the pathogenesis of other cancers. Genes Chromosomes Cancer. 1993 Jul;7(3):169–172. doi: 10.1002/gcc.2870070310. [DOI] [PubMed] [Google Scholar]
  32. Vogelstein B., Fearon E. R., Kern S. E., Hamilton S. R., Preisinger A. C., Nakamura Y., White R. Allelotype of colorectal carcinomas. Science. 1989 Apr 14;244(4901):207–211. doi: 10.1126/science.2565047. [DOI] [PubMed] [Google Scholar]
  33. Weinberg R. A. Tumor suppressor genes. Science. 1991 Nov 22;254(5035):1138–1146. doi: 10.1126/science.1659741. [DOI] [PubMed] [Google Scholar]
  34. Weissenbach J., Gyapay G., Dib C., Vignal A., Morissette J., Millasseau P., Vaysseix G., Lathrop M. A second-generation linkage map of the human genome. Nature. 1992 Oct 29;359(6398):794–801. doi: 10.1038/359794a0. [DOI] [PubMed] [Google Scholar]
  35. zur Hausen H. Papillomaviruses in anogenital cancer as a model to understand the role of viruses in human cancers. Cancer Res. 1989 Sep 1;49(17):4677–4681. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES