NIH Research Festival
One in four deaths in the United States is due to cancer despite an emphasis on prevention, early detection, and treatment. Further improvements in survival rates are likely to come from improving the limits of detection sensitivity at earlier stages of cancer. Apoptotic and necrotic cells release their DNA as fragments, which can be collected non-invasively as cell free DNA (cfDNA) from patient blood, stool, urine or sputum. In a similar fashion, tumor cells release circulating tumor DNA (ctDNA), which contains genetic and epigenetic signatures specific to the tumor. One epigenetic hallmark of many cancer types is differential DNA methylation at multiple loci compared to healthy tissue. Thus, detection and assessment of the methylation state of ctDNA at a specific locus could be utilized as an effective cancer diagnostic. We have recently identified the CpG island promoter region of ZNF154 as a hypermethylated locus in 15 solid epithelial tumor types, making it a promising pan-cancer biomarker. We utilized an ultra-sensitive method to detect methylated DNA fragments and applied this method to plasma and stool samples. Plasma samples from patients with ovarian cancer had significantly more fractions of densely methylated ZNF154 compared to healthy controls. Stool samples from patients with colorectal tubular adenomas also contained densely methylated ZNF154. Thus, hypermethylation at ZNF154 is a versatile pan-cancer biomarker that can be detected in multiple sample sources. We will expand this study to additional cancer types and compare complementary methods for sensitive detection of rare ctDNA methylated DNA fragments.
Scientific Focus Area: Cancer Biology
This page was last updated on Friday, March 26, 2021