Multiomic analysis of microRNA-mediated regulation reveals a proliferative axis involving miR-10b in fibrolamellar carcinoma.

Fibrolamellar carcinoma (FLC) is an aggressive liver cancer primarily afflicting adolescents and young adults. Most patients with FLC harbor a heterozygous deletion on chromosome 19 that leads to the oncogenic gene fusion, DNAJB1-PRKACA. There are currently no effective therapeutics for FLC.

In Utero Fetal Therapy: Stem Cells, Cell Transplantation, Gene Therapy, and CRISPR-Cas9.

In utero fetal therapy offers the opportunity to prevent and treat diseases with a cellular or genetic basis. Components of successful fetal treatment include isolation of a replacement cell population, in utero stem cell transplantation, cell engraftment with fetal immune tolerance, and ongoing cell function. Fetal gene therapy with CRISPR-Cas9 represents an exciting potential therapy for genetic diseases not amenable to gene supplementation via adenoviral vector transduction.

Hotspots of Aberrant Enhancer Activity in Fibrolamellar Carcinoma Reveal Candidate Oncogenic Pathways and Therapeutic Vulnerabilities.

Fibrolamellar carcinoma (FLC) is a rare, therapeutically intractable liver cancer that disproportionately affects youth. Although FLC tumors exhibit a distinct gene expression profile, the chromatin regulatory landscape and the genes most critical for tumor cell survival remain unclear. Here, we use chromatin run-on sequencing to discover ∼7,000 enhancers and 141 enhancer hotspots activated in FLC relative to nonmalignant liver.