Dr Shusterman on a DNA Methylome Enrichment Platform for Early Detection of Solid Tumors

Michael Shusterman, MD, clinical assistant professor, Department of Medicine, NYU Long Island School of Medicine, discusses findings from a retrospective study to determine the feasibility of a novel genome-wide methylome enrichment platform for the early detection of multiple solid tumors.

This study included samples of cell-free DNA extracted from the plasma of patients with 1 of 12 cancer types who had not yet begun treatment. These samples were compared with age- and sex-matched control samples from people with no known cancer diagnosis. All samples were analyzed with a bisulfate-free, non-degradative DNA methylome enrichment platform.

The interim training readout of this platform showed that the methylation assay distinguished cancer biopsies from non-cancer control biopsies with an overall area under the curve (AUC) of 0.94. Additionally, the assay distinguished a subset of typically low-shedding cancers, including bladder cancer, breast cancer, endometrial cancer, prostate cancer, and renal cancer, from non-cancer controls with an AUC of 0.91.

Traditional liquid biopsy sequencing platforms, such as next-generation sequencing, look for specific genes, such as KRAS, and detect the frequency of those genes in the blood, Shusterman says. However, many assays, including the DNA methylome enrichment platform used in this study, use epigenomic strategies to detect methylation patterns instead of gene frequency, Shusterman explains.

All cells, including cancer cells, use methylation patterns with unique signatures to activate and deactivate various transcriptional regions in the genome, Shusterman notes. This methylation enrichment test evaluates a variety of proprietary signatures to detect sets of DNA methylation sequences in several solid tumor types. Rather than detecting the presence of specific genes, if this test detects a certain proportion of a DNA methylation sequence in a liquid biopsy, that biopsy is considered positive for the respective tumor, Shusterman says.

This DNA methylation detection technology is becoming increasingly available, and commercialized assays use a similar approach, Shusterman concludes.