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British Journal of Cancer logoLink to British Journal of Cancer
. 2000 Dec;83(12):1659–1663. doi: 10.1054/bjoc.2000.1509

Progressive genetic aberrations detected by comparative genomic hybridization in squamous cell cervical cancer

D G Allen 1, D J White 2, A-M Hutchins 2, J P Scurry 3, S N Tabrizi 4, S M Garland 4, J E Armes 2,5
PMCID: PMC2363460  PMID: 11104563

Abstract

Genetic changes orchestrated by human papillomaviruses are the most important known factors in carcinogenesis of the uterine cervix. However, it is clear that additional genetic events are necessary for tumour progression. We have used comparative genomic hybridization to document non-random chromosomal gains and losses within a subset of 37 cervical carcinomas matched for clinical stage Ib, but with different lymph node status. There were significantly more chromosomal changes in the primary tumours when the lymph nodes were positive for metastases. The most frequent copy number alterations were loss of 3p, 11q, 6q and 10q and gain of 3q. The smallest areas of loss and gain on chromosome 3 were 3p14–22 and 3q24–26. The study identifies progressive DNA copy number changes associated with early-stage invasive cervical cancers with and without lymph node metastases, a factor of potential prognostic and therapeutic value. © 2000 Cancer Research Campaign http://www.bjcancer.com

Keywords: comparative genomic hybridization, cervix cancer, lymph node metastasis, human papillomavirus

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Selected References

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  1. Aubele M., Zitzelsberger H., Schenck U., Walch A., Höfler H., Werner M. Distinct cytogenetic alterations in squamous intraepithelial lesions of the cervix revealed by laser-assisted microdissection and comparative genomic hybridization. Cancer. 1998 Dec 25;84(6):375–379. doi: 10.1002/(sici)1097-0142(19981225)84:6<375::aid-cncr10>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]
  2. Bauer H. M., Ting Y., Greer C. E., Chambers J. C., Tashiro C. J., Chimera J., Reingold A., Manos M. M. Genital human papillomavirus infection in female university students as determined by a PCR-based method. JAMA. 1991 Jan 23;265(4):472–477. [PubMed] [Google Scholar]
  3. Dellas A., Torhorst J., Jiang F., Proffitt J., Schultheiss E., Holzgreve W., Sauter G., Mihatsch M. J., Moch H. Prognostic value of genomic alterations in invasive cervical squamous cell carcinoma of clinical stage IB detected by comparative genomic hybridization. Cancer Res. 1999 Jul 15;59(14):3475–3479. [PubMed] [Google Scholar]
  4. Dürst M., Dzarlieva-Petrusevska R. T., Boukamp P., Fusenig N. E., Gissmann L. Molecular and cytogenetic analysis of immortalized human primary keratinocytes obtained after transfection with human papillomavirus type 16 DNA. Oncogene. 1987;1(3):251–256. [PubMed] [Google Scholar]
  5. Heselmeyer K., Macville M., Schröck E., Blegen H., Hellström A. C., Shah K., Auer G., Ried T. Advanced-stage cervical carcinomas are defined by a recurrent pattern of chromosomal aberrations revealing high genetic instability and a consistent gain of chromosome arm 3q. Genes Chromosomes Cancer. 1997 Aug;19(4):233–240. [PubMed] [Google Scholar]
  6. Heselmeyer K., Schröck E., du Manoir S., Blegen H., Shah K., Steinbeck R., Auer G., Ried T. Gain of chromosome 3q defines the transition from severe dysplasia to invasive carcinoma of the uterine cervix. Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):479–484. doi: 10.1073/pnas.93.1.479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Isola J. J., Kallioniemi O. P., Chu L. W., Fuqua S. A., Hilsenbeck S. G., Osborne C. K., Waldman F. M. Genetic aberrations detected by comparative genomic hybridization predict outcome in node-negative breast cancer. Am J Pathol. 1995 Oct;147(4):905–911. [PMC free article] [PubMed] [Google Scholar]
  8. Kersemaekers A. M., Hermans J., Fleuren G. J., van de Vijver M. J. Loss of heterozygosity for defined regions on chromosomes 3, 11 and 17 in carcinomas of the uterine cervix. Br J Cancer. 1998;77(2):192–200. doi: 10.1038/bjc.1998.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kirchhoff M., Rose H., Petersen B. L., Maahr J., Gerdes T., Lundsteen C., Bryndorf T., Kryger-Baggesen N., Christensen L., Engelholm S. A. Comparative genomic hybridization reveals a recurrent pattern of chromosomal aberrations in severe dysplasia/carcinoma in situ of the cervix and in advanced-stage cervical carcinoma. Genes Chromosomes Cancer. 1999 Feb;24(2):144–150. doi: 10.1002/(sici)1098-2264(199902)24:2<144::aid-gcc7>3.0.co;2-9. [DOI] [PubMed] [Google Scholar]
  10. Kuukasjärvi T., Tanner M., Pennanen S., Karhu R., Visakorpi T., Isola J. Optimizing DOP-PCR for universal amplification of small DNA samples in comparative genomic hybridization. Genes Chromosomes Cancer. 1997 Feb;18(2):94–101. [PubMed] [Google Scholar]
  11. Larson A. A., Liao S. Y., Stanbridge E. J., Cavenee W. K., Hampton G. M. Genetic alterations accumulate during cervical tumorigenesis and indicate a common origin for multifocal lesions. Cancer Res. 1997 Oct 1;57(19):4171–4176. [PubMed] [Google Scholar]
  12. Liaw K. L., Glass A. G., Manos M. M., Greer C. E., Scott D. R., Sherman M., Burk R. D., Kurman R. J., Wacholder S., Rush B. B. Detection of human papillomavirus DNA in cytologically normal women and subsequent cervical squamous intraepithelial lesions. J Natl Cancer Inst. 1999 Jun 2;91(11):954–960. doi: 10.1093/jnci/91.11.954. [DOI] [PubMed] [Google Scholar]
  13. Martimbeau P. W., Kjorstad K. E., Iversen T. Stage IB carcinoma of the cervix, the Norwegian Radium hospital. II. Results when pelvic nodes are involved. Obstet Gynecol. 1982 Aug;60(2):215–218. [PubMed] [Google Scholar]
  14. Moch H., Presti J. C., Jr, Sauter G., Buchholz N., Jordan P., Mihatsch M. J., Waldman F. M. Genetic aberrations detected by comparative genomic hybridization are associated with clinical outcome in renal cell carcinoma. Cancer Res. 1996 Jan 1;56(1):27–30. [PubMed] [Google Scholar]
  15. Resnick R. M., Cornelissen M. T., Wright D. K., Eichinger G. H., Fox H. S., ter Schegget J., Manos M. M. Detection and typing of human papillomavirus in archival cervical cancer specimens by DNA amplification with consensus primers. J Natl Cancer Inst. 1990 Sep 19;82(18):1477–1484. doi: 10.1093/jnci/82.18.1477. [DOI] [PubMed] [Google Scholar]
  16. Ried T., Just K. E., Holtgreve-Grez H., du Manoir S., Speicher M. R., Schröck E., Latham C., Blegen H., Zetterberg A., Cremer T. Comparative genomic hybridization of formalin-fixed, paraffin-embedded breast tumors reveals different patterns of chromosomal gains and losses in fibroadenomas and diploid and aneuploid carcinomas. Cancer Res. 1995 Nov 15;55(22):5415–5423. [PubMed] [Google Scholar]
  17. Ried T., Petersen I., Holtgreve-Grez H., Speicher M. R., Schröck E., du Manoir S., Cremer T. Mapping of multiple DNA gains and losses in primary small cell lung carcinomas by comparative genomic hybridization. Cancer Res. 1994 Apr 1;54(7):1801–1806. [PubMed] [Google Scholar]
  18. Schröck E., Thiel G., Lozanova T., du Manoir S., Meffert M. C., Jauch A., Speicher M. R., Nürnberg P., Vogel S., Jänisch W. Comparative genomic hybridization of human malignant gliomas reveals multiple amplification sites and nonrandom chromosomal gains and losses. Am J Pathol. 1994 Jun;144(6):1203–1218. [PMC free article] [PubMed] [Google Scholar]
  19. Steenbergen R. D., Hermsen M. A., Walboomers J. M., Meijer G. A., Baak J. P., Meijer C. J., Snijders P. J. Non-random allelic losses at 3p, 11p and 13q during HPV-mediated immortalization and concomitant loss of terminal differentiation of human keratinocytes. Int J Cancer. 1998 May 4;76(3):412–417. doi: 10.1002/(sici)1097-0215(19980504)76:3<412::aid-ijc20>3.0.co;2-b. [DOI] [PubMed] [Google Scholar]
  20. Tanaka H., Shimizu M., Horikawa I., Kugoh H., Yokota J., Barrett J. C., Oshimura M. Evidence for a putative telomerase repressor gene in the 3p14.2-p21.1 region. Genes Chromosomes Cancer. 1998 Oct;23(2):123–133. doi: 10.1002/(sici)1098-2264(199810)23:2<123::aid-gcc5>3.0.co;2-4. [DOI] [PubMed] [Google Scholar]
  21. Telenius H., Carter N. P., Bebb C. E., Nordenskjöld M., Ponder B. A., Tunnacliffe A. Degenerate oligonucleotide-primed PCR: general amplification of target DNA by a single degenerate primer. Genomics. 1992 Jul;13(3):718–725. doi: 10.1016/0888-7543(92)90147-k. [DOI] [PubMed] [Google Scholar]
  22. Wistuba I. I., Montellano F. D., Milchgrub S., Virmani A. K., Behrens C., Chen H., Ahmadian M., Nowak J. A., Muller C., Minna J. D. Deletions of chromosome 3p are frequent and early events in the pathogenesis of uterine cervical carcinoma. Cancer Res. 1997 Aug 1;57(15):3154–3158. [PubMed] [Google Scholar]

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