Identification of a Common Site of Provirus Integration in Radiation Leukemia Virus-Induced T-Cell Lymphomas in Mice

Lambert, Jacques; Bergeron, Dominique; Kozak, Christine A.; Rassart, Éric

doi:10.1006/viro.1999.9992

Cited by 2 publications

(2 citation statements)

References 25 publications

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“…This event triggers reprogramming of cell proliferation, apoptosis, differentiation, metabolism, epigenetic reorganization, and genomic instability (21). These changes can support the integration of episomal HPV genomes into chromosomes of the host cell (19,33) and contribute to further overexpression of the viral genes E6 and E7 (20,28). This is consistent with an increase of the high-risk E7 protein levels during early steps of carcinogenesis in cells of the cervical squamous epithelium (11).…”

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confidence: 59%

Detection of Human Papillomavirus Type 18 E7 Oncoprotein in Cervical Smears: a Feasibility Study

et al. 2012

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Persistent infections by high-risk human papillomaviruses (HPVs) are the main etiological factor for cervical cancer, and expression of HPV E7 oncoproteins was suggested to be a potential marker for tumor progression. The objective of this study was to generate new reagents for the detection of the HPV18 E7 oncoprotein in cervical smears. Rabbit monoclonal antibodies against recombinant E7 protein of HPV type 18 (HPV18) were generated and characterized using Western blotting, epitope mapping, indirect immunofluorescence, and immunohistochemistry. One clone specifically recognizing HPV18 E7 was used for the development of a sandwich enzyme-linked immunosorbent assay (ELISA). The assay was validated using recombinant E7 proteins of various HPV types and lysates from E7-positive cervical carcinoma cells. A total of 14 HPV18 DNA-positive cervical swab specimens and 24 HPV DNA-negative-control specimens were used for the determination of E7 protein levels by the newly established sandwich ELISA. On the basis of the average absorbance values obtained from all 24 negative controls, a cutoff above which a clinical sample can be judged E7 positive was established. Significant E7 signals 6-to 30-fold over background were found in 7 out of 14 abnormal HPV18 DNA-positive cervical smear specimens. This feasibility study demonstrates for the first time that HPV18 E7 oncoprotein can be detected in cervical smears. P ersistent infections by human papillomaviruses (HPVs) are the main etiologic factor for cervical cancer (41). Approximately 85% of cervical cancers are squamous cell carcinomas (SCCs) which arise from dividing keratinocytes in the squamous epithelium of the ectocervix and 15% are adenocarcinomas (ACs) which arise from glandular cells located in the endocervix (3, 25). About 40 HPV genotypes that can infect epithelial squamous and glandular cells in the cervical mucosa have been described. On the basis of epidemiological and biochemical data, only a subgroup of HPV types, referred to as high-risk HPVs, is associated with intraepithelial lesions that have a high potential for progression to invasive carcinoma. Infections by high-risk HPV genotypes have been detected in virtually all cervical cancers (37). At least 15 highrisk HPV types have been associated with these cancers. HPV type 16 (HPV16) and HPV18 are the most prevalent genotypes worldwide in SCCs as well as in ACs (23).A persistent infection with oncogenic HPVs is necessary for the development of cervical precancer and cancer (3, 37, 40, 41). Initial events of cervical carcinogenesis after viral infection by highrisk HPV types are specific changes that overcome the transcriptional control of viral gene expression in the infected keratinocytes (40). Inactivation of these cellular control functions permits deregulated transcription of the early viral genes E6 and E7. This event triggers reprogramming of cell proliferation, apoptosis, differentiation, metabolism, epigenetic reorganization, and genomic instability (21). These changes can support the integration ...

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confidence: 59%

Detection of Human Papillomavirus Type 18 E7 Oncoprotein in Cervical Smears: a Feasibility Study

et al. 2012

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“…Southern blot analysis of DNA from RadLV/VL3-induced tumors with a U3 long terminal repeat probe or a T-cell receptor (TcR) probe has already been performed and these studies show that RadLV tumors are clonal cell populations (2,35,70). However, these studies did not allow to determine if the total cell population was homogenous.…”

Section: Resultsmentioning

confidence: 99%

Radiation Leukemia Virus Common Integration at the Kis2 Locus: Simultaneous Overexpression of a Novel Noncoding RNA and of the Proximal Phf6 Gene

Landais

Quantin

Rassart

2005

J Virol

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Retroviral tagging has been used extensively and successfully to identify genes implicated in cancer pathways. In order to find oncogenes implicated in T-cell leukemia, we used the highly leukemogenic radiation leukemia retrovirus VL3 (RadLV/VL3). We applied the inverted PCR technique to isolate and analyze sequences flanking proviral integrations in RadLV/VL3-induced T lymphomas. We found retroviral integrations in c-myc and Pim1 as already reported but we also identified for the first time Notch1 as a RadLV common integration site. More interestingly, we found a new RadLV common integration site that is situated on mouse chromosome X (XA4 region, bp 45091000). This site has also been reported as an SL3-3 and Moloney murine leukemia virus integration site, which strengthens its implication in murine leukemia virus-induced T lymphomas. This locus, named Kis2 (Kaplan Integration Site 2), was found rearranged in 11% of the tumors analyzed. In this article, we report not only the alteration of the Kis2 gene located nearby in response to RadLV integration but also the induction of the expression of Phf6, situated about 250 kbp from the integration site. The Kis2 gene encodes five different alternatively spliced noncoding RNAs and the Phf6 gene codes for a 365-amino-acid protein which contains two plant homology domain fingers, recently implicated in the Börje-son-Forssman-Lehmann syndrome in humans. With the recent release of the mouse genome sequence, highthroughput retroviral tagging emerges as a powerful tool in the quest for oncogenes. It also allows the analysis of large DNA regions surrounding the integration locus.

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Identification of a Common Site of Provirus Integration in Radiation Leukemia Virus-Induced T-Cell Lymphomas in Mice

Cited by 2 publications

References 25 publications

Detection of Human Papillomavirus Type 18 E7 Oncoprotein in Cervical Smears: a Feasibility Study

Detection of Human Papillomavirus Type 18 E7 Oncoprotein in Cervical Smears: a Feasibility Study

Radiation Leukemia Virus Common Integration at the Kis2 Locus: Simultaneous Overexpression of a Novel Noncoding RNA and of the Proximal Phf6 Gene

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