Abstract: The present invention provides arrays for gene loci that allow diagnosis of cervical cancer in patients who may be asymptomatic or have inconclusive Pap smears or cytology, and allowing earlier diagnosis and treatment of the subject. The present invention also provides methods of determination of a global promoter DNA methylation in a cervical tissue sample from a subject, using a variety of methods which can detect DNA methylation. Further, the invention provides methods of diagnosis of cervical cancer in a subject, by comparing the global promoter DNA methylation in a cervical tissue sample obtained from a subject to the global promoter DNA methylation of standard controls.

Abstract: Differentially methylated oral squamous cell carcinoma (OSCC) biomarkers, identified in-vitro and validated in well-characterized surgical specimens, have shown poor clinical correlation in cohorts with different risk profiles. To overcome this lack of relevance we used the HumanMethylation27 BeadChip, publicly available methylation and expression array data, and Quantitative Methylation Specific PCR to uncover differential methylation in OSCC clinical samples with heterogeneous risk profiles. A two stage-design consisting of Discovery and Prevalence screens was used to identify differential promoter methylation and deregulated pathways in patients diagnosed with OSCC and head and neck squamous cell carcinoma. This Phase I Biomarker Development Trial identified a panel of differentially methylated genes in normal and OSCC clinical samples from patients with heterogeneous risk profiles. This panel may be useful for early detection and cancer prevention studies.

Abstract: The present invention provides arrays for gene loci that allow diagnosis of cervical cancer in patients who may be asymptomatic or have inconclusive Pap smears or cytology, and allowing earlier diagnosis and treatment of the subject. The present invention also provides methods of determination of a global promoter DNA methylation in a cervical tissue sample from a subject, using a variety of methods which can detect DNA methylation. Further, the invention provides methods of diagnosis of cervical cancer in a subject, by comparing the global promoter DNA methylation in a cervical tissue sample obtained from a subject to the global promoter DNA methylation of standard controls.

Abstract: Pap smears and HPV infection tests do not distinguish between lesions that will progress to an invasive carcinoma and those that will not. We aimed to identify epigenetic biomarkers for diagnosis and progression monitoring of premalignant lesions in cervical cancer. Hypermethylated genes were identified as potential biomarkers after validation by MSP, including GGTLA4 and ZNF516. The methylation frequency for these two genes was higher in tumor: GGTLA4 (100%) and ZNF516 (96%); than in normal samples: GGTLA4 (12%) and ZNF516 (16%). The methylation status of GGTLA4 showed a progression in methylation frequency from normal samples to invasive carcinoma. The immunohistochemical expression was lower in tumor for both: GGTLA4 (50.8%) and ZNF516 (66.2%); than in normal samples: GGTLA4 (71.2%) and ZNF516 (88.1%) (p<0.05). In conclusion, we identified methylation biomarkers for the molecular screening and characterization of cervical cancer.

Abstract: Pap smears and HPV infection tests do not distinguish between lesions that will progress to an invasive carcinoma and those that will not. We aimed to identify epigenetic biomarkers for diagnosis and progression monitoring of premalignant lesions in cervical cancer. Hypermethylated genes were identified as potential biomarkers after validation by MSP, including GGTLA4 and ZNF516. The methylation frequency for these two genes was higher in tumor: GGTLA4 (100%) and ZNF516 (96%); than in normal samples: GGTLA4 (12%) and ZNF516 (16%). The methylation status of GGTLA4 showed a progression in methylation frequency from normal samples to invasive carcinoma. The immunohistochemical expression was lower in tumor for both: GGTLA4 (50.8%) and ZNF516 (66.2%); than in normal samples: GGTLA4 (71.2%) and ZNF516 (88.1%) (p<0.05). In conclusion, we identified methylation biomarkers for the molecular screening and characterization of cervical cancer.

Abstract: Differentially methylated oral squamous cell carcinoma (OSCC) biomarkers, identified in-vitro and validated in well-characterized surgical specimens, have shown poor clinical correlation in cohorts with different risk profiles. To overcome this lack of relevance we used the HumanMethylation27 BeadChip, publicly available methylation and expression array data, and Quantitative Methylation Specific PCR to uncover differential methylation in OSCC clinical samples with heterogeneous risk profiles. A two stage-design consisting of Discovery and Prevalence screens was used to identify differential promoter methylation and deregulated pathways in patients diagnosed with OSCC and head and neck squamous cell carcinoma. This Phase I Biomarker Development Trial identified a panel of differentially methylated genes in normal and OSCC clinical samples from patients with heterogeneous risk profiles. This panel may be useful for early detection and cancer prevention studies.