The DOI matches its Crossref record; 20 of the 20 references it cites were found in a registry or an index.
In situ detection of the hypermethylation-induced inactivation of the p16 gene as an early event in oncogenesis
Open accessAbstract
We have developed a technique, methylation-specific PCR in situ hybridization (MSP-ISH), which allows for the methylation status of specific DNA sequences to be visualized in individual cells. We use MSP-ISH to monitor the timing and consequences of aberrant hypermethylation of the p16 tumor suppresser gene during the progression of cancers of the lung and cervix. Hypermethylation of p16 was localized only to the neoplastic cells in both in situ lesions and invasive cancers, and was associated with loss of p16 protein expression. MSP-ISH allowed us to dissect the surprising finding that p16 hypermethylation occurs in cervical carcinoma. This tumor is associated with infection of the oncogenic human papillomavirus, which expresses a protein, E7, that inactivates the retinoblastoma (Rb) protein. Thus, simultaneous Rb and p16 inactivation would not be needed to abrogate the critical cyclin D–Rb pathway. MSP-ISH reveals that p16 hypermethylation occurs heterogeneously within early cervical tumor cell populations that are separate from those expressing viral E7 transcripts. In advanced cervical cancers, the majority of cells have a hypermethylated p16 , lack p16 protein, but no longer express E7. These data suggest that p16 inactivation is selected as the most effective mechanism of blocking the cyclin D–Rb pathway during the evolution of an invasive cancer from precursor lesions. These studies demonstrate that MSP-ISH is a powerful approach for studying the dynamics of aberrant methylation of critical tumor suppressor genes during tumor evolution.
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Self-citationThe E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53
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The human papilloma virus-16 E7-oncoprotein is able to bind to the retinoblastoma gene product
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Self-citationAlterations in DNA Methylation: A Fundamental Aspect of Neoplasia
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Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma
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Self-citationSilencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma.
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Cited by
The fundamental role of epigenetic events in cancer
Jones, P. A., & Baylin, S. B. (2002) · Nature Reviews Genetics · doi:10.1038/nrg816 · Cited by 5,648
Self-citationGene Silencing in Cancer in Association with Promoter Hypermethylation
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Self-citationEpigenetic gene silencing in cancer – a mechanism for early oncogenic pathway addiction?
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Self-citationDNA hypermethylation in tumorigenesis: epigenetics joins genetics
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Self-citationDNA Methylation: A Profile of Methods and Applications
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Metadata
- Authors
- Nuovo, G. J., Plaia, T. W., Belinsky, S. A., Baylin, S. B., & Herman, J. G.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1999-10-26
- Volume
- 96
- Issue
- 22
- Pages
- 12754-12759
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2032052720
- Cited by
- 314
- References
- 20
- FWCI
- 7.29
- Type
- journal article
- Language
- en
- Open access
- green
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- Nuovo, G. J., Plaia, T. W., Belinsky, S. A., Baylin, S. B., & Herman, J. G. (1999). In situ detection of the hypermethylation-induced inactivation of the p16 gene as an early event in oncogenesis. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.96.22.12754
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