Detection and monitoring of translocation renal cell carcinoma via plasma cell-free epigenomic profiling

Translocation renal cell carcinoma (tRCC) is an aggressive fusion-driven subtype of kidney cancer that is frequently misdiagnosed due to morphologic overlap with other kidney cancer subtypes. Conventional liquid biopsy assays targeting DNA alterations are suboptimal for use in tRCC due to its paucity of genomic changes. We demonstrate the utility of cell-free chromatin profiling to noninvasively detect and monitor tRCC with high accuracy, a method that could have applicability to other genomically quiet cancers. Overall design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for histone modifications H3K27ac, and H3K4me3, methylated immunoprecipitation and high-throughput sequencing (MeDIP-seq), and low pass whole genome sequencing on cell-free DNA.