Logo of brjcancerBJC HomepageBJC Advance online publicationBJC Current IssueSubmitting an article to BJCWeb feeds
Br J Cancer. 1999 Aug; 80(12): 2008–2018.
PMCID: PMC2374277

The molecular genetics of cervical carcinoma


In the pathogenesis of cervical carcinoma there are three major components, two of them related to the role of human papillomaviruses (HPV). First, the effect of viral E6 and E7 proteins. Second, the integration of viral DNA in chromosomal regions associated with well known tumour phenotypes. Some of these viral integrations occur recurrently at specific chromosomal locations, such as 8q24 and 12q15, both harbouring HPV18 and HPV16. And third, there are other recurrent genetic alterations not linked to HPV. Recurrent losses of heterozygosity (LOH) have been detected in chromosome regions 3p14–22, 4p16, 5p15, 6p21–22, 11q23, 17p13.3 without effect on p53, 18q12–22 and 19q13, all of them suggesting the alteration of putative tumour suppressor genes not yet identified. Recurrent amplification has been mapped to 3q+ arm, with the common region in 3q24–28 in 90% of invasive carcinomas. The mutator phenotype, microsatellite instability, plays a minor role and is detected in only 7% of cervical carcinomas. The development of cervical carcinoma requires the sequential occurrence and selection of several genetic alterations. The identification of the specific genes involved, and their correlation with specific tumour properties and stages could improve the understanding and perhaps the management of cervical carcinoma. © 1999 Cancer Research Campaign

Keywords: cervical carcinoma, genetic damage, papillomavirus, viral integration, LOH

Full Text

The Full Text of this article is available as a PDF (153K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Antinore MJ, Birrer MJ, Patel D, Nader L, McCance DJ. The human papillomavirus type 16 E7 gene product interacts with and trans-activates the AP1 family of transcription factors. EMBO J. 1996 Apr 15;15(8):1950–1960. [PMC free article] [PubMed]
  • Atkin NB, Baker MC, Fox MF. Chromosome changes in 43 carcinomas of the cervix uteri. Cancer Genet Cytogenet. 1990 Feb;44(2):229–241. [PubMed]
  • Banks L, Edmonds C, Vousden KH. Ability of the HPV16 E7 protein to bind RB and induce DNA synthesis is not sufficient for efficient transforming activity in NIH3T3 cells. Oncogene. 1990 Sep;5(9):1383–1389. [PubMed]
  • Bartholomew JS, Glenville S, Sarkar S, Burt DJ, Stanley MA, Ruiz-Cabello F, Chengang J, Garrido F, Stern PL. Integration of high-risk human papillomavirus DNA is linked to the down-regulation of class I human leukocyte antigens by steroid hormones in cervical tumor cells. Cancer Res. 1997 Mar 1;57(5):937–942. [PubMed]
  • Bartsch D, Boye B, Baust C, zur Hausen H, Schwarz E. Retinoic acid-mediated repression of human papillomavirus 18 transcription and different ligand regulation of the retinoic acid receptor beta gene in non-tumorigenic and tumorigenic HeLa hybrid cells. EMBO J. 1992 Jun;11(6):2283–2291. [PMC free article] [PubMed]
  • Bauer-Hofmann R, Borghouts C, Auvinen E, Bourda E, Rösl F, Alonso A. Genomic cloning and characterization of the nonoccupied allele corresponding to the integration site of human papillomavirus type 16 DNA in the cervical cancer cell line SiHa. Virology. 1996 Mar 1;217(1):33–41. [PubMed]
  • Bethwaite PB, Koreth J, Herrington CS, McGee JO. Loss of heterozygosity occurs at the D11S29 locus on chromosome 11q23 in invasive cervical carcinoma. Br J Cancer. 1995 Apr;71(4):814–818. [PMC free article] [PubMed]
  • Bosch FX, Manos MM, Muñoz N, Sherman M, Jansen AM, Peto J, Schiffman MH, Moreno V, Kurman R, Shah KV. Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group. J Natl Cancer Inst. 1995 Jun 7;87(11):796–802. [PubMed]
  • Braly P. Preventing cervical cancer. Nat Med. 1996 Jul;2(7):749–751. [PubMed]
  • Cannistra SA, Niloff JM. Cancer of the uterine cervix. N Engl J Med. 1996 Apr 18;334(16):1030–1038. [PubMed]
  • Castrén K, Vähäkangas K, Heikkinen E, Ranki A. Absence of p53 mutations in benign and pre-malignant male genital lesions with over-expressed p53 protein. Int J Cancer. 1998 Aug 31;77(5):674–678. [PubMed]
  • Couturier J, Sastre-Garau X, Schneider-Maunoury S, Labib A, Orth G. Integration of papillomavirus DNA near myc genes in genital carcinomas and its consequences for proto-oncogene expression. J Virol. 1991 Aug;65(8):4534–4538. [PMC free article] [PubMed]
  • Cullen AP, Reid R, Campion M, Lörincz AT. Analysis of the physical state of different human papillomavirus DNAs in intraepithelial and invasive cervical neoplasm. J Virol. 1991 Feb;65(2):606–612. [PMC free article] [PubMed]
  • Chen TM, Pecoraro G, Defendi V. Genetic analysis of in vitro progression of human papillomavirus-transfected human cervical cells. Cancer Res. 1993 Mar 1;53(5):1167–1171. [PubMed]
  • Choo KB, Lee HH, Liew LN, Chong KY, Chou HF. Analysis of the unoccupied site of an integrated human papillomavirus 16 sequence in a cervical carcinoma. Virology. 1990 Oct;178(2):621–625. [PubMed]
  • Choo KB, Huang CJ, Chen CM, Han CP, Au LC. Jun-B oncogene aberrations in cervical cancer cell lines. Cancer Lett. 1995 Jul 13;93(2):249–253. [PubMed]
  • Chu TY, Shen CY, Chiou YS, Lu JJ, Perng CL, Yu MS, Liu HS. HPV-associated cervical cancers show frequent allelic loss at 3p14 but no apparent aberration of FHIT mRNA. Int J Cancer. 1998 Jan 19;75(2):199–204. [PubMed]
  • Dokianakis DN, Sourvinos G, Sakkas S, Athanasiadou E, Spandidos DA. Detection of HPV and ras gene mutations in cervical smears from female genital lesions. Oncol Rep. 1998 Sep-Oct;5(5):1195–1198. [PubMed]
  • Dowhanick JJ, McBride AA, Howley PM. Suppression of cellular proliferation by the papillomavirus E2 protein. J Virol. 1995 Dec;69(12):7791–7799. [PMC free article] [PubMed]
  • Dürst M, Croce CM, Gissmann L, Schwarz E, Huebner K. Papillomavirus sequences integrate near cellular oncogenes in some cervical carcinomas. Proc Natl Acad Sci U S A. 1987 Feb;84(4):1070–1074. [PMC free article] [PubMed]
  • el Awady MK, Kaplan JB, O'Brien SJ, Burk RD. Molecular analysis of integrated human papillomavirus 16 sequences in the cervical cancer cell line SiHa. Virology. 1987 Aug;159(2):389–398. [PubMed]
  • Frattini MG, Hurst SD, Lim HB, Swaminathan S, Laimins LA. Abrogation of a mitotic checkpoint by E2 proteins from oncogenic human papillomaviruses correlates with increased turnover of the p53 tumor suppressor protein. EMBO J. 1997 Jan 15;16(2):318–331. [PMC free article] [PubMed]
  • Fujita M, Inoue M, Tanizawa O, Iwamoto S, Enomoto T. Alterations of the p53 gene in human primary cervical carcinoma with and without human papillomavirus infection. Cancer Res. 1992 Oct 1;52(19):5323–5328. [PubMed]
  • Gallego MI, Lazo PA. Deletion in human chromosome region 12q13-15 by integration of human papillomavirus DNA in a cervical carcinoma cell line. J Biol Chem. 1995 Oct 13;270(41):24321–24326. [PubMed]
  • Gallego MI, Schoenmakers EF, Van de Ven WJ, Lazo PA. Complex genomic rearrangement within the 12q15 multiple aberration region induced by integrated human papillomavirus 18 in a cervical carcinoma cell line. Mol Carcinog. 1997 Jun;19(2):114–121. [PubMed]
  • Gloss B, Chong T, Bernard HU. Numerous nuclear proteins bind the long control region of human papillomavirus type 16: a subset of 6 of 23 DNase I-protected segments coincides with the location of the cell-type-specific enhancer. J Virol. 1989 Mar;63(3):1142–1152. [PMC free article] [PubMed]
  • Greenblatt MS, Bennett WP, Hollstein M, Harris CC. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res. 1994 Sep 15;54(18):4855–4878. [PubMed]
  • Greenspan DL, Connolly DC, Wu R, Lei RY, Vogelstein JT, Kim YT, Mok JE, Muñoz N, Bosch FX, Shah K, et al. Loss of FHIT expression in cervical carcinoma cell lines and primary tumors. Cancer Res. 1997 Nov 1;57(21):4692–4698. [PubMed]
  • Hampton GM, Larson AA, Baergen RN, Sommers RL, Kern S, Cavenee WK. Simultaneous assessment of loss of heterozygosity at multiple microsatellite loci using semi-automated fluorescence-based detection: subregional mapping of chromosome 4 in cervical carcinoma. Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6704–6709. [PMC free article] [PubMed]
  • Hampton GM, Penny LA, Baergen RN, Larson A, Brewer C, Liao S, Busby-Earle RM, Williams AW, Steel CM, Bird CC, et al. Loss of heterozygosity in cervical carcinoma: subchromosomal localization of a putative tumor-suppressor gene to chromosome 11q22-q24. Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):6953–6957. [PMC free article] [PubMed]
  • Hayashi S, Tanimoto K, Hajiro-Nakanishi K, Tsuchiya E, Kurosumi M, Higashi Y, Imai K, Suga K, Nakachi K. Abnormal FHIT transcripts in human breast carcinomas: a clinicopathological and epidemiological analysis of 61 Japanese cases. Cancer Res. 1997 May 15;57(10):1981–1985. [PubMed]
  • Helland A, Børresen-Dale AL, Peltomäki P, Hektoen M, Kristensen GB, Nesland JM, de la Chapelle A, Lothe RA. Microsatellite instability in cervical and endometrial carcinomas. Int J Cancer. 1997 Mar 4;70(5):499–501. [PubMed]
  • Helland A, Karlsen F, Due EU, Holm R, Kristensen G, Børresen-Dale A l. Mutations in the TP53 gene and protein expression of p53, MDM 2 and p21/WAF-1 in primary cervical carcinomas with no or low human papillomavirus load. Br J Cancer. 1998 Jul;78(1):69–72. [PMC free article] [PubMed]
  • Helland A, Olsen AO, Gjøen K, Akselsen HE, Sauer T, Magnus P, Børresen-Dale AL, Rønningen KS. An increased risk of cervical intra-epithelial neoplasia grade II-III among human papillomavirus positive patients with the HLA-DQA1*0102-DQB1*0602 haplotype: a population-based case-control study of Norwegian women. Int J Cancer. 1998 Mar 30;76(1):19–24. [PubMed]
  • 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. [PMC free article] [PubMed]
  • Heselmeyer K, Macville M, Schröck E, Blegen H, Hellström AC, 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]
  • Hueber AO, Zörnig M, Lyon D, Suda T, Nagata S, Evan GI. Requirement for the CD95 receptor-ligand pathway in c-Myc-induced apoptosis. Science. 1997 Nov 14;278(5341):1305–1309. [PubMed]
  • Huettner PC, Gerhard DS, Li L, Gersell DJ, Dunnigan K, Kamarasova T, Rader JS. Loss of heterozygosity in clinical stage IB cervical carcinoma: relationship with clinical and histopathologic features. Hum Pathol. 1998 Apr;29(4):364–370. [PubMed]
  • Iglesias M, Yen K, Gaiotti D, Hildesheim A, Stoler MH, Woodworth CD. Human papillomavirus type 16 E7 protein sensitizes cervical keratinocytes to apoptosis and release of interleukin-1alpha. Oncogene. 1998 Sep 10;17(10):1195–1205. [PubMed]
  • Jeon S, Lambert PF. Integration of human papillomavirus type 16 DNA into the human genome leads to increased stability of E6 and E7 mRNAs: implications for cervical carcinogenesis. Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1654–1658. [PMC free article] [PubMed]
  • Jeon S, Allen-Hoffmann BL, Lambert PF. Integration of human papillomavirus type 16 into the human genome correlates with a selective growth advantage of cells. J Virol. 1995 May;69(5):2989–2997. [PMC free article] [PubMed]
  • Jones MH, Nakamura Y. Deletion mapping of chromosome 3p in female genital tract malignancies using microsatellite polymorphisms. Oncogene. 1992 Aug;7(8):1631–1634. [PubMed]
  • Kaelbling M, Burk RD, Atkin NB, Johnson AB, Klinger HP. Loss of heterozygosity on chromosome 17p and mutant p53 in HPV-negative cervical carcinomas. Lancet. 1992 Jul 18;340(8812):140–142. [PubMed]
  • Kalantari M, Karlsen F, Kristensen G, Holm R, Hagmar B, Johansson B. Disruption of the E1 and E2 reading frames of HPV 16 in cervical carcinoma is associated with poor prognosis. Int J Gynecol Pathol. 1998 Apr;17(2):146–153. [PubMed]
  • Kamijo T, Zindy F, Roussel MF, Quelle DE, Downing JR, Ashmun RA, Grosveld G, Sherr CJ. Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19ARF. Cell. 1997 Nov 28;91(5):649–659. [PubMed]
  • Karlsen F, Rabbitts PH, Sundresan V, Hagmar B. PCR-RFLP studies on chromosome 3p in formaldehyde-fixed, paraffin-embedded cervical cancer tissues. Int J Cancer. 1994 Sep 15;58(6):787–792. [PubMed]
  • Kersemaekers AM, Hermans J, Fleuren GJ, van de Vijver MJ. 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. [PMC free article] [PubMed]
  • Kersemaekers AM, Kenter GG, Hermans J, Fleuren GJ, van de Vijver MJ. Allelic loss and prognosis in carcinoma of the uterine cervix. Int J Cancer. 1998 Aug 21;79(4):411–417. [PubMed]
  • Kim JW, Namkoong SE, Ryu SW, Kim HS, Shin JW, Lee JM, Kim DH, Kim IK. Absence of p15INK4B and p16INK4A gene alterations in primary cervical carcinoma tissues and cell lines with human papillomavirus infection. Gynecol Oncol. 1998 Jul;70(1):75–79. [PubMed]
  • Kinzler KW, Vogelstein B. Lessons from hereditary colorectal cancer. Cell. 1996 Oct 18;87(2):159–170. [PubMed]
  • Kinzler KW, Vogelstein B. Landscaping the cancer terrain. Science. 1998 May 15;280(5366):1036–1037. [PubMed]
  • Kirchhoff M, Rose H, Petersen BL, Maahr J, Gerdes T, Lundsteen C, Bryndorf T, Kryger-Baggesen N, Christensen L, Engelholm SA, et al. 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. [PubMed]
  • Kohno T, Takayama H, Hamaguchi M, Takano H, Yamaguchi N, Tsuda H, Hirohashi S, Vissing H, Shimizu M, Oshimura M, et al. Deletion mapping of chromosome 3p in human uterine cervical cancer. Oncogene. 1993 Jul;8(7):1825–1832. [PubMed]
  • Koi M, Morita H, Yamada H, Satoh H, Barrett JC, Oshimura M. Normal human chromosome 11 suppresses tumorigenicity of human cervical tumor cell line SiHa. Mol Carcinog. 1989;2(1):12–21. [PubMed]
  • Konishi H, Takahashi T, Kozaki K, Yatabe Y, Mitsudomi T, Fujii Y, Sugiura T, Matsuda H, Takahashi T, Takahashi T. Detailed deletion mapping suggests the involvement of a tumor suppressor gene at 17p13.3, distal to p53, in the pathogenesis of lung cancers. Oncogene. 1998 Oct 22;17(16):2095–2100. [PubMed]
  • Krammer PH. The tumor strikes back: new data on expression of the CD95(APO-1/Fas) receptor/ligand system may cause paradigm changes in our view on drug treatment and tumor immunology. Cell Death Differ. 1997 Jul;4(5):362–364. [PubMed]
  • Ku JL, Kim WH, Park HS, Kang SB, Park JG. Establishment and characterization of 12 uterine cervical-carcinoma cell lines: common sequence variation in the E7 gene of HPV-16-positive cell lines. Int J Cancer. 1997 Jul 17;72(2):313–320. [PubMed]
  • Ku WH, Liu IL, Yen MS, Chang Chien CC, Yue CT, Ma YY, Chang SF, Ng HT, Wu CW, Shen CY. Genomic deletion and p53 inactivation in cervical carcinoma. Int J Cancer. 1997 Jul 17;72(2):270–276. [PubMed]
  • Kurvinen K, Syrjänen K, Syrjänen S. p53 and bcl-2 proteins as prognostic markers in human papillomavirus-associated cervical lesions. J Clin Oncol. 1996 Jul;14(7):2120–2130. [PubMed]
  • Larson AA, Kern S, Sommers RL, Yokota J, Cavenee WK, Hampton GM. Analysis of replication error (RER+) phenotypes in cervical carcinoma. Cancer Res. 1996 Mar 15;56(6):1426–1431. [PubMed]
  • Larson AA, Kern S, Curtiss S, Gordon R, Cavenee WK, Hampton GM. High resolution analysis of chromosome 3p alterations in cervical carcinoma. Cancer Res. 1997 Sep 15;57(18):4082–4090. [PubMed]
  • Lazo PA. Human papillomaviruses in oncogenesis. Bioessays. 1988 Nov;9(5):158–162. [PubMed]
  • Lazo PA. Rearrangement of both alleles of human chromosome 8 in HeLa cells, one of them as a result of papillomavirus DNA integration. J Biol Chem. 1988 Jan 5;263(1):360–367. [PubMed]
  • Lazo PA, Gallego MI, Ballester S, Feduchi E. Genetic alterations by human papillomaviruses in oncogenesis. FEBS Lett. 1992 Mar 30;300(2):109–113. [PubMed]
  • Le Beau MM, Drabkin H, Glover TW, Gemmill R, Rassool FV, McKeithan TW, Smith DI. An FHIT tumor suppressor gene? Genes Chromosomes Cancer. 1998 Apr;21(4):281–289. [PubMed]
  • Leis PF, Stevens KR, Baer SC, Kadmon D, Goldberg LH, Wang XJ. A c-rasHa mutation in the metastasis of a human papillomavirus (HPV)-18 positive penile squamous cell carcinoma suggests a cooperative effect between HPV-18 and c-rasHa activation in malignant progression. Cancer. 1998 Jul 1;83(1):122–129. [PubMed]
  • Lengauer C, Kinzler KW, Vogelstein B. Genetic instabilities in human cancers. Nature. 1998 Dec 17;396(6712):643–649. [PubMed]
  • Lopez-Borges S, Gallego MI, Lazo PA. Recurrent integration of papillomavirus DNA within the human 12q14-15 uterine breakpoint region in genital carcinomas. Genes Chromosomes Cancer. 1998 Sep;23(1):55–60. [PubMed]
  • Mao L, Fan YH, Lotan R, Hong WK. Frequent abnormalities of FHIT, a candidate tumor suppressor gene, in head and neck cancer cell lines. Cancer Res. 1996 Nov 15;56(22):5128–5131. [PubMed]
  • Mitelman F, Mertens F, Johansson B. A breakpoint map of recurrent chromosomal rearrangements in human neoplasia. Nat Genet. 1997 Apr;15(Spec No):417–474. [PubMed]
  • Mitra AB, Murty VV, Li RG, Pratap M, Luthra UK, Chaganti RS. Allelotype analysis of cervical carcinoma. Cancer Res. 1994 Aug 15;54(16):4481–4487. [PubMed]
  • Mitra AB, Murty VV, Pratap M, Sodhani P, Chaganti RS. ERBB2 (HER2/neu) oncogene is frequently amplified in squamous cell carcinoma of the uterine cervix. Cancer Res. 1994 Feb 1;54(3):637–639. [PubMed]
  • Montgomery KD, Tedford KL, McDougall JK. Genetic instability of chromosome 3 in HPV-immortalized and tumorigenic human keratinocytes. Genes Chromosomes Cancer. 1995 Oct;14(2):97–105. [PubMed]
  • Muller CY, O'Boyle JD, Fong KM, Wistuba II, Biesterveld E, Ahmadian M, Miller DS, Gazdar AF, Minna JD. Abnormalities of fragile histidine triad genomic and complementary DNAs in cervical cancer: association with human papillomavirus type. J Natl Cancer Inst. 1998 Mar 18;90(6):433–439. [PubMed]
  • Mullokandov MR, Kholodilov NG, Atkin NB, Burk RD, Johnson AB, Klinger HP. Genomic alterations in cervical carcinoma: losses of chromosome heterozygosity and human papilloma virus tumor status. Cancer Res. 1996 Jan 1;56(1):197–205. [PubMed]
  • Ning Y, Weber JL, Killary AM, Ledbetter DH, Smith JR, Pereira-Smith OM. Genetic analysis of indefinite division in human cells: evidence for a cell senescence-related gene(s) on human chromosome 4. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5635–5639. [PMC free article] [PubMed]
  • O'Connor MJ, Tan SH, Tan CH, Bernard HU. YY1 represses human papillomavirus type 16 transcription by quenching AP-1 activity. J Virol. 1996 Oct;70(10):6529–6539. [PMC free article] [PubMed]
  • Oshimura M, Kugoh H, Koi M, Shimizu M, Yamada H, Satoh H, Barrett JC. 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. [PubMed]
  • Park SY, Kang YS, Kim BG, Lee SH, Lee ED, Lee KH, Park KB, Lee JH. Loss of heterozygosity on the short arm of chromosome 17 in uterine cervical carcinomas. Cancer Genet Cytogenet. 1995 Jan;79(1):74–78. [PubMed]
  • Pinion SB, Kennedy JH, Miller RW, MacLean AB. Oncogene expression in cervical intraepithelial neoplasia and invasive cancer of cervix. Lancet. 1991 Apr 6;337(8745):819–820. [PubMed]
  • Pirisi L, Yasumoto S, Feller M, Doniger J, DiPaolo JA. Transformation of human fibroblasts and keratinocytes with human papillomavirus type 16 DNA. J Virol. 1987 Apr;61(4):1061–1066. [PMC free article] [PubMed]
  • Popescu NC, DiPaolo JA. Preferential sites for viral integration on mammalian genome. Cancer Genet Cytogenet. 1989 Oct 15;42(2):157–171. [PubMed]
  • Popescu NC, DiPaolo JA, Amsbaugh SC. Integration sites of human papillomavirus 18 DNA sequences on HeLa cell chromosomes. Cytogenet Cell Genet. 1987;44(1):58–62. [PubMed]
  • Rabbitts TH. Chromosomal translocations in human cancer. Nature. 1994 Nov 10;372(6502):143–149. [PubMed]
  • Rabbitts TH. Chromosomal breakpoints hit the spot. Nat Med. 1997 May;3(5):496–497. [PubMed]
  • Rösl F, Achtstätter T, Bauknecht T, Hutter KJ, Futterman G, zur Hausen H. Extinction of the HPV18 upstream regulatory region in cervical carcinoma cells after fusion with non-tumorigenic human keratinocytes under non-selective conditions. EMBO J. 1991 Jun;10(6):1337–1345. [PMC free article] [PubMed]
  • Sánchez-García I. Consequences of chromosomal abnormalities in tumor development. Annu Rev Genet. 1997;31:429–453. [PubMed]
  • Sastre-Garau X, Couturier J, Favre M, Orth G. A recurrent human papillomavirus integration site at chromosome region 12q14-q15 in SW756 and SK-v cell lines derived from genital tumors. C R Acad Sci III. 1995 Apr;318(4):475–478. [PubMed]
  • Saxon PJ, Srivatsan ES, Stanbridge EJ. Introduction of human chromosome 11 via microcell transfer controls tumorigenic expression of HeLa cells. EMBO J. 1986 Dec 20;5(13):3461–3466. [PMC free article] [PubMed]
  • Schneider JF, McGlennen RC, LaBresh KV, Ostrow RS, Faras AJ. Rhesus papillomavirus type 1 cooperates with activated ras in transforming primary epithelial rat cells independent of dexamethasone. J Virol. 1991 Jun;65(6):3354–3358. [PMC free article] [PubMed]
  • Smith PP, Friedman CL, Bryant EM, McDougall JK. Viral integration and fragile sites in human papillomavirus-immortalized human keratinocyte cell lines. Genes Chromosomes Cancer. 1992 Sep;5(2):150–157. [PubMed]
  • Southern SA, Herrington CS. Interphase karyotypic analysis of chromosomes 11, 17 and X in invasive squamous-cell carcinoma of the cervix: morphological correlation with HPV infection. Int J Cancer. 1997 Mar 4;70(5):502–507. [PubMed]
  • Sozzi G, Veronese ML, Negrini M, Baffa R, Cotticelli MG, Inoue H, Tornielli S, Pilotti S, De Gregorio L, Pastorino U, et al. The FHIT gene 3p14.2 is abnormal in lung cancer. Cell. 1996 Apr 5;85(1):17–26. [PubMed]
  • Srivatsan ES, Misra BC, Venugopalan M, Wilczynski SP. 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]
  • Steenbergen RD, Hermsen MA, Walboomers JM, Joenje H, Arwert F, Meijer CJ, Snijders PJ. Integrated human papillomavirus type 16 and loss of heterozygosity at 11q22 and 18q21 in an oral carcinoma and its derivative cell line. Cancer Res. 1995 Nov 15;55(22):5465–5471. [PubMed]
  • Steenbergen RD, Walboomers JM, Meijer CJ, van der Raaij-Helmer EM, Parker JN, Chow LT, Broker TR, Snijders PJ. Transition of human papillomavirus type 16 and 18 transfected human foreskin keratinocytes towards immortality: activation of telomerase and allele losses at 3p, 10p, 11q and/or 18q. Oncogene. 1996 Sep 19;13(6):1249–1257. [PubMed]
  • Stöppler H, Stöppler MC, Johnson E, Simbulan-Rosenthal CM, Smulson ME, Iyer S, Rosenthal DS, Schlegel R. The E7 protein of human papillomavirus type 16 sensitizes primary human keratinocytes to apoptosis. Oncogene. 1998 Sep 10;17(10):1207–1214. [PubMed]
  • Thiagalingam S, Lisitsyn NA, Hamaguchi M, Wigler MH, Willson JK, Markowitz SD, Leach FS, Kinzler KW, Vogelstein B. Evaluation of the FHIT gene in colorectal cancers. Cancer Res. 1996 Jul 1;56(13):2936–2939. [PubMed]
  • Thomas M, Matlashewski G, Pim D, Banks L. Induction of apoptosis by p53 is independent of its oligomeric state and can be abolished by HPV-18 E6 through ubiquitin mediated degradation. Oncogene. 1996 Jul 18;13(2):265–273. [PubMed]
  • Tomlinson I, Bodmer W. Selection, the mutation rate and cancer: ensuring that the tail does not wag the dog. Nat Med. 1999 Jan;5(1):11–12. [PubMed]
  • Tomlinson IP, Novelli MR, Bodmer WF. The mutation rate and cancer. Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14800–14803. [PMC free article] [PubMed]
  • Uejima H, Mitsuya K, Kugoh H, Horikawa I, Oshimura M. Normal human chromosome 2 induces cellular senescence in the human cervical carcinoma cell line SiHa. Genes Chromosomes Cancer. 1995 Oct;14(2):120–127. [PubMed]
  • Unger ER, Vernon SD, Thoms WW, Nisenbaum R, Spann CO, Horowitz IR, Icenogle JP, Reeves WC. Human papillomavirus and disease-free survival in FIGO stage Ib cervical cancer. J Infect Dis. 1995 Nov;172(5):1184–1190. [PubMed]
  • Vernon SD, Unger ER, Miller DL, Lee DR, Reeves WC. Association of human papillomavirus type 16 integration in the E2 gene with poor disease-free survival from cervical cancer. Int J Cancer. 1997 Feb 20;74(1):50–56. [PubMed]
  • Werness BA, Levine AJ, Howley PM. Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science. 1990 Apr 6;248(4951):76–79. [PubMed]
  • Wilke CM, Hall BK, Hoge A, Paradee W, Smith DI, Glover TW. FRA3B extends over a broad region and contains a spontaneous HPV16 integration site: direct evidence for the coincidence of viral integration sites and fragile sites. Hum Mol Genet. 1996 Feb;5(2):187–195. [PubMed]
  • Yokota J, Tsukada Y, Nakajima T, Gotoh M, Shimosato Y, Mori N, Tsunokawa Y, Sugimura T, Terada M. Loss of heterozygosity on the short arm of chromosome 3 in carcinoma of the uterine cervix. Cancer Res. 1989 Jul 1;49(13):3598–3601. [PubMed]
  • Yoshino K, Enomoto T, Nakamura T, Nakashima R, Wada H, Saitoh J, Noda K, Murata Y. Aberrant FHIT transcripts in squamous cell carcinoma of the uterine cervix. Int J Cancer. 1998 Apr 13;76(2):176–181. [PubMed]
  • Zimonjic DB, Popescu ND, DiPaolo JA. Chromosomal organization of viral integration sites in human papillomavirus-immortalized human keratinocyte cell lines. Cancer Genet Cytogenet. 1994 Jan;72(1):39–43. [PubMed]
  • Zimonjic DB, Druck T, Ohta M, Kastury K, Croce CM, Popescu NC, Huebner K. Positions of chromosome 3p14.2 fragile sites (FRA3B) within the FHIT gene. Cancer Res. 1997 Mar 15;57(6):1166–1170. [PubMed]
  • Zou TT, Lei J, Shi YQ, Yin J, Wang S, Souza RF, Kong D, Shimada Y, Smolinski KN, Greenwald BD, et al. FHIT gene alterations in esophageal cancer and ulcerative colitis (UC). Oncogene. 1997 Jul 3;15(1):101–105. [PubMed]
  • zur Hausen H, de Villiers EM. Human papillomaviruses. Annu Rev Microbiol. 1994;48:427–447. [PubMed]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...