Host-cell DNA methylation patterns during high-risk HPV-induced carcinogenesis reveal a heterogeneous nature of cervical pre-cancer
Cervical cancer development following a persistent infection with high-risk human papillomavirus (hrHPV) is driven by additional host-cell changes, such as altered DNA methylation. In previous studies, we have identified 12 methylated host genes associated with cervical cancer and pre-cancer (CIN2/3...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-07-01
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| Series: | Epigenetics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/15592294.2018.1507197 |
| _version_ | 1797678887207960576 |
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| author | Wina Verlaat Robert W. Van Leeuwen Putri W. Novianti Ed Schuuring Chris J. L. M. Meijer Ate G. J. Van Der Zee Peter J. F. Snijders Daniëlle A. M. Heideman Renske D. M. Steenbergen G. Bea A. Wisman |
| author_facet | Wina Verlaat Robert W. Van Leeuwen Putri W. Novianti Ed Schuuring Chris J. L. M. Meijer Ate G. J. Van Der Zee Peter J. F. Snijders Daniëlle A. M. Heideman Renske D. M. Steenbergen G. Bea A. Wisman |
| author_sort | Wina Verlaat |
| collection | DOAJ |
| description | Cervical cancer development following a persistent infection with high-risk human papillomavirus (hrHPV) is driven by additional host-cell changes, such as altered DNA methylation. In previous studies, we have identified 12 methylated host genes associated with cervical cancer and pre-cancer (CIN2/3). This study systematically analyzed the onset and DNA methylation pattern of these genes during hrHPV-induced carcinogenesis using a longitudinal in vitro model of hrHPV-transformed cell lines (n = 14) and hrHPV-positive cervical scrapings (n = 113) covering various stages of cervical carcinogenesis. DNA methylation analysis was performed by quantitative methylation-specific PCR (qMSP) and relative qMSP values were used to analyze the data. The majority of genes displayed a comparable DNA methylation pattern in both cell lines and clinical specimens. DNA methylation onset occurred at early or late immortal passage, and DNA methylation levels gradually increased towards tumorigenic cells. Subsequently, we defined a so-called cancer-like methylation-high pattern based on the DNA methylation levels observed in cervical scrapings from women with cervical cancer. This cancer-like methylation-high pattern was observed in 72% (38/53) of CIN3 and 55% (11/20) of CIN2, whereas it was virtually absent in hrHPV-positive controls (1/26). In conclusion, hrHPV-induced carcinogenesis is characterized by early onset of DNA methylation, typically occurring at the pre-tumorigenic stage and with highest DNA methylation levels at the cancer stage. Host-cell DNA methylation patterns in cervical scrapings from women with CIN2 and CIN3 are heterogeneous, with a subset displaying a cancer-like methylation-high pattern, suggestive for a higher cancer risk. |
| first_indexed | 2024-03-11T23:06:27Z |
| format | Article |
| id | doaj.art-575a5320a27447d395adaf3cea223c0e |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-11T23:06:27Z |
| publishDate | 2018-07-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-575a5320a27447d395adaf3cea223c0e2023-09-21T13:09:21ZengTaylor & Francis GroupEpigenetics1559-22941559-23082018-07-0113776977810.1080/15592294.2018.15071971507197Host-cell DNA methylation patterns during high-risk HPV-induced carcinogenesis reveal a heterogeneous nature of cervical pre-cancerWina Verlaat0Robert W. Van Leeuwen1Putri W. Novianti2Ed Schuuring3Chris J. L. M. Meijer4Ate G. J. Van Der Zee5Peter J. F. Snijders6Daniëlle A. M. Heideman7Renske D. M. Steenbergen8G. Bea A. Wisman9Cancer Center AmsterdamUniversity of Groningen, University Medical Center Groningen, Cancer Research Center GroningenCancer Center AmsterdamUniversity of Groningen, University Medical Center Groningen, Cancer Research Center GroningenCancer Center AmsterdamUniversity of Groningen, University Medical Center Groningen, Cancer Research Center GroningenCancer Center AmsterdamCancer Center AmsterdamCancer Center AmsterdamUniversity of Groningen, University Medical Center Groningen, Cancer Research Center GroningenCervical cancer development following a persistent infection with high-risk human papillomavirus (hrHPV) is driven by additional host-cell changes, such as altered DNA methylation. In previous studies, we have identified 12 methylated host genes associated with cervical cancer and pre-cancer (CIN2/3). This study systematically analyzed the onset and DNA methylation pattern of these genes during hrHPV-induced carcinogenesis using a longitudinal in vitro model of hrHPV-transformed cell lines (n = 14) and hrHPV-positive cervical scrapings (n = 113) covering various stages of cervical carcinogenesis. DNA methylation analysis was performed by quantitative methylation-specific PCR (qMSP) and relative qMSP values were used to analyze the data. The majority of genes displayed a comparable DNA methylation pattern in both cell lines and clinical specimens. DNA methylation onset occurred at early or late immortal passage, and DNA methylation levels gradually increased towards tumorigenic cells. Subsequently, we defined a so-called cancer-like methylation-high pattern based on the DNA methylation levels observed in cervical scrapings from women with cervical cancer. This cancer-like methylation-high pattern was observed in 72% (38/53) of CIN3 and 55% (11/20) of CIN2, whereas it was virtually absent in hrHPV-positive controls (1/26). In conclusion, hrHPV-induced carcinogenesis is characterized by early onset of DNA methylation, typically occurring at the pre-tumorigenic stage and with highest DNA methylation levels at the cancer stage. Host-cell DNA methylation patterns in cervical scrapings from women with CIN2 and CIN3 are heterogeneous, with a subset displaying a cancer-like methylation-high pattern, suggestive for a higher cancer risk.http://dx.doi.org/10.1080/15592294.2018.1507197cervical carcinogenesisdna methylation markerscervical scrapingsin vitro modelhrhpvquantitative methylation-specific pcr (qmsp)epigenetics |
| spellingShingle | Wina Verlaat Robert W. Van Leeuwen Putri W. Novianti Ed Schuuring Chris J. L. M. Meijer Ate G. J. Van Der Zee Peter J. F. Snijders Daniëlle A. M. Heideman Renske D. M. Steenbergen G. Bea A. Wisman Host-cell DNA methylation patterns during high-risk HPV-induced carcinogenesis reveal a heterogeneous nature of cervical pre-cancer Epigenetics cervical carcinogenesis dna methylation markers cervical scrapings in vitro model hrhpv quantitative methylation-specific pcr (qmsp) epigenetics |
| title | Host-cell DNA methylation patterns during high-risk HPV-induced carcinogenesis reveal a heterogeneous nature of cervical pre-cancer |
| title_full | Host-cell DNA methylation patterns during high-risk HPV-induced carcinogenesis reveal a heterogeneous nature of cervical pre-cancer |
| title_fullStr | Host-cell DNA methylation patterns during high-risk HPV-induced carcinogenesis reveal a heterogeneous nature of cervical pre-cancer |
| title_full_unstemmed | Host-cell DNA methylation patterns during high-risk HPV-induced carcinogenesis reveal a heterogeneous nature of cervical pre-cancer |
| title_short | Host-cell DNA methylation patterns during high-risk HPV-induced carcinogenesis reveal a heterogeneous nature of cervical pre-cancer |
| title_sort | host cell dna methylation patterns during high risk hpv induced carcinogenesis reveal a heterogeneous nature of cervical pre cancer |
| topic | cervical carcinogenesis dna methylation markers cervical scrapings in vitro model hrhpv quantitative methylation-specific pcr (qmsp) epigenetics |
| url | http://dx.doi.org/10.1080/15592294.2018.1507197 |
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