Disruption of the E1 and E2 Reading Frames of HPV 16 in Cervical Carcinoma Is Associated with Poor Prognosis

Kalantari, Mina; Karlsen, Frank; Kristensen, Gunnar B.; Holm, Ruth; Hagmar, Björn; Johansson, Bo

doi:10.1097/00004347-199804000-00009

Cited by 126 publications

(133 citation statements)

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“…30 There were no obvious associations between sequence changes in E2 or E6 and physical state in this series. Eight of the 11 isolates containing only integrated viral DNA were disrupted in E2, a proportion similar to that reported by Kalantari et al; 31 but interestingly, half of the cases were integrated at the 3Ј end of E2, whereas in the …”

Section: Discussionsupporting

confidence: 82%

Sequence variation and physical state of human papillomavirus type 16 cervical cancer isolates from Australia and New Caledonia

Watts

Thompson

Cossart

et al. 2001

Intl Journal of Cancer

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Section: Discussionsupporting

confidence: 82%

Sequence variation and physical state of human papillomavirus type 16 cervical cancer isolates from Australia and New Caledonia

Watts

Thompson

Cossart

et al. 2001

Intl Journal of Cancer

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“…During the process of integration, deletions and/or rearrangements typically occur within the HPV genome that selectively retain expression of the E6 and E7 genes, underscoring the importance of the continued expression of these genes in the maintenance of the malignant phenotype. This is consistent with the observation that cells with integrated HPV have a selective growth advantage and that E2 damage is associated with poor prognosis and shortened disease-free survival (Jeon et al, 1995;Vernon et al, 1997;Kalantari et al, 1998).…”

Section: Introductionsupporting

confidence: 88%

Common fragile sites are preferential targets for HPV16 integrations in cervical tumors

Thorland¹,

Myers²,

et al. 2003

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The development of cervical cancer is highly associated with human papillomavirus (HPV) infection. HPV integration into the genome of infected cervical cells is temporally associated with the acquisition of the malignant phenotype. A relationship between the sites of HPV integration in cervical cancer and the position of the common fragile sites (CFSs) has been observed at both the cytogenetic and molecular levels. To further explore this relationship at the molecular level, we used RS-PCR to rapidly isolate cellular sequences flanking the sites of HPV16 integration in 26 primary cervical tumors. Human bacterial artificial chromosome clones were isolated based on these flanking sequences and used as probes for fluorescence in situ hybridization on aphidicolin-stimulated metaphases. Our data demonstrate that 11/23 HPV16 integrations in cervical tumors occurred within CFSs (Po0.001). In addition, we show that deletions and complex rearrangements frequently occur in the cellular sequences targeted by the integrations and that integrations cluster in FRA13C (13q22), FRA3B (3p14.2), and FRA17B (17q23). Finally, our data suggest that cellular genes, such as Notch 1, are disrupted by the HPV16 integrations, which may contribute to the malignant phenotype.

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“…Under physiological conditions, the free Rb protein liberated from the disrupted complex has a feedback effect on p16 expression [29]. Since the E2 polypeptide binds to LCR (Table 3), the presence of E2 in cells carrying the episomal HPV DNA may efficiently control the transcription of mRNA encoding the E6/E7 oncoproteins [30]. In contrast, the cells carrying an integrated HPV genome would stop producing the E2 polypeptide due to disruption of the E2 ORF.…”

Section: Overexpression Of the P16/ink4a Polypeptide In Hpv Transformmentioning

confidence: 99%

Diagnostic role of p16/INK4A protein in Human Papillomavirus (HPV) induced cervical dysplasia

Rajčáni¹,

Adamkov²,

et al. 2010

Open Life Sciences

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Abstract:The p16/INK4A protein is a cellular regulatory polypeptide over-expressed in the presence of high levels of the Human Papillomavirus (HPV) coded E7 protein. This review outlines the use of p16 antigen staining in cervical biopsies as well as in PAP smears summarizing the corresponding literature and commenting the authors' own experience. The p16 antigen is a reliable marker for dysplastic cells in CINII/CINIII (HSIL) lesions as viewed in cervical biopsies. When PAP smears were examined at large scale screening for p16 antigenreactive and atypical cells, considerable variations could be found especially in ASCUS graded lesions. Therefore, the presence of p16-reactive atypical cells in PAP smears should be interpreted together with the cytological signs of dysplasia, such as the altered N/C ratio. In addition, women revealing p16-positive ASCUS/LSIL specimens should be examined for the presence of HPV DNA. Detection of HPV DNA alone, i.e. in the absence of cytological screening has a low predictive value, since the clearance of HPV may occur even in the absence of morphological alterations. Combined cytological as well as molecular follow up contributes to the efficiency of diagnostic and increases the probability of correct interpretation of the pre-cancerous lesions by non-invasive techniques.

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Disruption of the E1 and E2 Reading Frames of HPV 16 in Cervical Carcinoma Is Associated with Poor Prognosis

Cited by 126 publications

References 0 publications

Sequence variation and physical state of human papillomavirus type 16 cervical cancer isolates from Australia and New Caledonia

Sequence variation and physical state of human papillomavirus type 16 cervical cancer isolates from Australia and New Caledonia

Common fragile sites are preferential targets for HPV16 integrations in cervical tumors

Diagnostic role of p16/INK4A protein in Human Papillomavirus (HPV) induced cervical dysplasia

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