DNA methylation profiling of cervical squamous intraepithelial lesions using liquid-based cytology specimens: an approach that utilizes receiver-operating characteristic analysis

Cancer
Karen S GustafsonDouglas P Clark

Abstract

Cervical carcinoma is a common malignancy among women worldwide, and its pathogenesis is related causally to human papillomavirus infection. The progression from precursor squamous intraepithelial lesions to cervical carcinoma requires additional genetic and epigenetic alterations that have not been characterized fully. The authors examined aberrant promoter methylation of multiple tumor suppressor genes in precursor squamous intraepithelial lesions. A multiplex, nested, methylation-specific polymerase chain reaction approach was used to examine promoter methylation of 15 tumor suppressor genes in high-grade squamous intraepithelial lesions (HSIL, n = 11), low-grade squamous intraepithelial lesions (LSIL, n = 17), and negative tissues (n = 11) from liquid-based cytology samples. The area under the receiver-operating characteristic (ROC) curve was determined for individual methylated tumor suppressor genes and for gene combinations to evaluate test performance for the ability of methylation profiles to distinguish HSIL cytology samples from combined LSIL/negative cytology samples. Aberrant promoter methylation of DAPK1 and IGSF4 occurred at a high frequency in HSIL samples and was absent in LSIL and negative samples. There was a...Continue Reading

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