Hotspots of aberrant enhancer activity in fibrolamellar carcinoma reveal molecular mechanisms of oncogenesis and intrinsic drug resistance

Timothy A. Dinh; Ramja Sritharan; F. Donelson Smith; Adam B. Francisco; Rosanna K. Ma; Rodica P. Bunaciu; Matt Kanke; Charles G. Danko; Andrew P. Massa; John D. Scott; Praveen Sethupathy

Fibrolamellar carcinoma is a devastating cancer affecting young adults with limited treatment options. Thus, there remains a great need to identify potential therapeutic targets. Here we have analyzed primary FLC tumors and matched NML samples to map the unique enhancer landscape of FLC. One of the goals of this study was to discover master regulators of dysregulated gene expression and signaling in FLC. We took advantage of the new technique (le)ChRO-seq (Chu et al., 2018) , which allowed us to perform run-on sequencing on frozen primary tumors. A notable advantage of (le)ChRO-seq is that it allows quantification of both enhancer activity and gene transcription from a single experiment, thereby avoiding possible confounders associated with using multiple different assays.