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MYC activation associated with the integration of HPV DNA at the MYC locus in genital tumors
Abstract
To determine whether integration of human papillomavirus (HPV) DNA sequences could lead to the deregulation of genes implied in oncogenesis, we analysed the HPV integration sites in a series of nine cell lines derived from invasive genital carcinomas. Using in situ hybridization, HPV16 or 18 sequences were found at chromosome band 8q24, the localization of MYC, in IC1, IC2, IC3, IC6 and CAC-1 cells and at other sites in IC4, IC5, IC7 and IC8 cells. We then localized viral sequences at the molecular level and searched for alterations of MYC structure and expression in these cells. MYC genomic status and viral integration sites were also analysed in primary tumors from which IC1, IC2, IC3 and IC6 cells were derived. In IC1, IC2 and CAC-1 cells, HPV DNA was located within 58 kb of MYC, downstream, upstream, or within MYC. In IC3 and IC6 cells, HPV DNA was located 400-500 kb upstream of MYC. Amplification studies showed that, in IC1, IC2 and IC3, viral and MYC sequences were co-amplified in an amplicon between less than 50 and 800 kb in size. MYC amplification was also observed in primary tumors, indicating that this genetic alteration, together with viral insertion at the MYC locus, had already taken place in vivo. MYC was not amplified in the other cell lines. MYC mRNA and protein overexpression was observed in the five cell lines in which the HPV DNA was inserted close to the MYC locus, but in none of the lines where the insertion had occurred at other sites. MYC activation, t…
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“Taken together, these data implicate viral integration as a strong activator of MYC expression29, acting in cis rather than trans and possibly mediated by the epithelial-specific viral enhancer amplified to CN 30 within the R1 repeat structure (Figure 2b)27.”
From The haplotype-resolved genome and epigenome of the aneuploid HeLa cancer cell line (2013) · cites this paper as [29]
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Cited by
The haplotype-resolved genome and epigenome of the aneuploid HeLa cancer cell line
Adey, A., Burton, J. N., Kitzman, J. O., Hiatt, J. B., Lewis, A. P., Martin, B. K., Qiu, R., Lee, C., & Shendure, J. (2013) · Nature · doi:10.1038/nature12064 · Cited by 362
Metadata
- Authors
- Peter, M., Rosty, C., Couturier, J., Radvanyi, F., Teshima, H., & Sastre-Garau, X.
- Venue
- Oncogene
- Published
- 2006-05-08
- Volume
- 25
- Issue
- 44
- Pages
- 5985-5993
- ISSN
- 0950-9232
- 1476-5594
- Cited by
- 114
- References
- 3
- Language
- en
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