TY - JOUR
T1 - Evaluation of candidate methylation markers to detect cervical neoplasia
AU - Shivapurkar, Narayan
AU - Sherman, Mark E.
AU - Stastny, Victor
AU - Echebiri, Chinyere
AU - Rader, Janet S.
AU - Nayar, Ritu
AU - Bonfiglio, Thomas A.
AU - Gazdar, Adi F.
AU - Wang, Sophia S.
N1 - Funding Information:
This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, and partially funded by CA95713 and CA94141.
PY - 2007/12
Y1 - 2007/12
N2 - Objective.: Studies of cervical cancer and its immediate precursor, cervical intraepithelial neoplasia 3 (CIN3), have identified genes that often show aberrant DNA methylation and therefore represent candidate early detection markers. We used quantitative PCR assays to evaluate methylation in five candidate genes (TNFRSF10C, DAPK1, SOCS3, HS3ST2 and CDH1) previously demonstrated as methylated in cervical cancer. Methods.: In this analysis, we performed methylation assays for the five candidate genes in 45 invasive cervical cancers, 12 histologically normal cervical specimens, and 23 liquid-based cervical cytology specimens confirmed by expert review as unequivocal demonstrating cytologic high-grade squamous intraepithelial lesions, thus representing the counterparts of histologic CIN3. Results.: We found hypermethylation of HS3ST2 in 93% of cancer tissues and 70% of cytology specimens interpreted as CIN3; hypermethylation of CDH1 was found in 89% of cancers and 26% of CIN3 cytology specimens. Methylation of either HS3ST2 or CDH1 was observed in 100% of cervical cancer tissues and 83% of CIN3 cytology specimens. None of the five genes showed detectable methylation in normal cervical tissues. Conclusion.: Our data support further evaluation of HS3ST2 and CDH1 methylation as potential markers of cervical cancer and its precursor lesions.
AB - Objective.: Studies of cervical cancer and its immediate precursor, cervical intraepithelial neoplasia 3 (CIN3), have identified genes that often show aberrant DNA methylation and therefore represent candidate early detection markers. We used quantitative PCR assays to evaluate methylation in five candidate genes (TNFRSF10C, DAPK1, SOCS3, HS3ST2 and CDH1) previously demonstrated as methylated in cervical cancer. Methods.: In this analysis, we performed methylation assays for the five candidate genes in 45 invasive cervical cancers, 12 histologically normal cervical specimens, and 23 liquid-based cervical cytology specimens confirmed by expert review as unequivocal demonstrating cytologic high-grade squamous intraepithelial lesions, thus representing the counterparts of histologic CIN3. Results.: We found hypermethylation of HS3ST2 in 93% of cancer tissues and 70% of cytology specimens interpreted as CIN3; hypermethylation of CDH1 was found in 89% of cancers and 26% of CIN3 cytology specimens. Methylation of either HS3ST2 or CDH1 was observed in 100% of cervical cancer tissues and 83% of CIN3 cytology specimens. None of the five genes showed detectable methylation in normal cervical tissues. Conclusion.: Our data support further evaluation of HS3ST2 and CDH1 methylation as potential markers of cervical cancer and its precursor lesions.
KW - Cervical cancer
KW - Promoter methylation
KW - Tumor suppressor genes
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U2 - 10.1016/j.ygyno.2007.08.057
DO - 10.1016/j.ygyno.2007.08.057
M3 - Article
C2 - 17894941
AN - SCOPUS:36348989016
SN - 0090-8258
VL - 107
SP - 549
EP - 553
JO - Gynecologic oncology
JF - Gynecologic oncology
IS - 3
ER -