Hi-C for genome-wide detection of enhancer-hijacking rearrangements in routine clinical biopsies of lymphoid cancers

We performed Hi-C retrospectively on archival formalin-fixed paraffin embedded (FFPE) tissue biopsies of lymphoid cancers to explore the utility of Hi-C for comprehensively identifying enhancer-hijacking oncogene rearrangements in routine clinical samples. Our data shows that FFPE-compatible Hi-C retains state-specific topological features of tumor cells at gene loci associated with germinal center B cell or plasma cell state and comprehensively detects rearrangements genome-wide with high concordance against prior clinical testing. Hi-C additionally reveals enhancer-promoter interactions consistent with enhancer-hijacking across rearrangement breakpoints at recurrent, uncommon, and diversely-rearranging loci, and provides topological information to support the interpretation of these events that is not provided by alternative routine clinical assays such as FISH. Overall design: Genome-wide chromatin conformation capture (Hi-C) performed on formalin-fixed paraffin-embedded tissue specimens of lymphoid cancers from patients *************************************************************** Raw files for human/patient samples were not submitted to GEO due to concerns about submitting personally identifiable sequence data for open access. ***************************************************************