TY - JOUR
T1 - Patterns of cellular and HPV 16 methylation as biomarkers for cervical neoplasia
AU - Patel, Divya A.
AU - Rozek, Laura S.
AU - Colacino, Justin A.
AU - Van Zomeren-Dohm, Adrienne
AU - Ruffin, Mack T.
AU - Unger, Elizabeth R.
AU - Dolinoy, Dana C.
AU - Swan, David C.
AU - Onyekwuluje, Juanita
AU - DeGraffinreid, Cecilia R.
AU - Paskett, Electra D.
N1 - Funding Information:
This work was supported by the National Cancer Institute (NCI) of the National Institutes of Health (grant numbers K07CA120040 to DAP, K24CA080846 to MTR and P50CA105632 to EDP). This work was also supported by the Behavioral Measurement Shared Resource at The Ohio State University Comprehensive Cancer Center (grant numbers P30CA016058 , K07CA107079 from NCI) and by NCI's Early Detection Research Network through IAA Y1-CN-5005-01 and Y1-CN-0101-01 . Support for JAC was provided by an Institutional Training Grant from the National Institute of Environmental Health Sciences (NIEHS) of the NIH (grant number T32 ES007062 ).
PY - 2012/9
Y1 - 2012/9
N2 - Aberrant promoter methylation of biologically relevant genes in cervical cancer and uneven CpG distribution within the human papillomavirus 16 (HPV 16) enhancer region have been reported. Cervical samples and questionnaires from 151 women screened for cervical cancer in Appalachian Ohio were analyzed. Methylation was measured by bisulfite sequencing in candidate gene sites in ESR1, DCC, p16, and LINE1 elements. Among 89 HPV 16-positive women, CpG sites in the E6 promoter and enhancer regions and the L1 region of the HPV 16 genome were measured. Methylation levels were compared by cervical cytology and HPV 16 status. HPV methylation was low regardless of cytology status, however E6 methylation was significantly higher in women with normal cytology. ESR1 and DCC methylation were significantly higher in HPV 16-positive women. Increased methylation at sites in the E6 promoter region was associated with lower odds of abnormal cytology. Increased methylation in candidate genes was associated with higher odds of abnormal cytology, particularly DCC region 2.4, DCC region 2.6, ESR1 region 3.2, and LINE1 site 1.2. HPV 16 genome CpG methylation was low except for the L1 region. In general, lower HPV 16 methylation and higher candidate gene methylation levels were associated with higher odds of abnormal cytology.
AB - Aberrant promoter methylation of biologically relevant genes in cervical cancer and uneven CpG distribution within the human papillomavirus 16 (HPV 16) enhancer region have been reported. Cervical samples and questionnaires from 151 women screened for cervical cancer in Appalachian Ohio were analyzed. Methylation was measured by bisulfite sequencing in candidate gene sites in ESR1, DCC, p16, and LINE1 elements. Among 89 HPV 16-positive women, CpG sites in the E6 promoter and enhancer regions and the L1 region of the HPV 16 genome were measured. Methylation levels were compared by cervical cytology and HPV 16 status. HPV methylation was low regardless of cytology status, however E6 methylation was significantly higher in women with normal cytology. ESR1 and DCC methylation were significantly higher in HPV 16-positive women. Increased methylation at sites in the E6 promoter region was associated with lower odds of abnormal cytology. Increased methylation in candidate genes was associated with higher odds of abnormal cytology, particularly DCC region 2.4, DCC region 2.6, ESR1 region 3.2, and LINE1 site 1.2. HPV 16 genome CpG methylation was low except for the L1 region. In general, lower HPV 16 methylation and higher candidate gene methylation levels were associated with higher odds of abnormal cytology.
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U2 - 10.1016/j.jviromet.2012.05.022
DO - 10.1016/j.jviromet.2012.05.022
M3 - Article
C2 - 22664184
AN - SCOPUS:84863845994
SN - 0166-0934
VL - 184
SP - 84
EP - 92
JO - Journal of Virological Methods
JF - Journal of Virological Methods
IS - 1-2
ER -
