Molecular characterization of hepatic epithelioid hemangioendothelioma reveals alterations in various genes involved in DNA repair, epigenetic regulation, signaling pathways, and cell cycle control

Epithelioid hemangioendotheliomas (EHE) of the liver are rare, low-malignant vascular tumors whose molecular pathogenesis is incompletely understood. The diagnosis of EHE is challenging, and the course of the disease can be highly variable. Therapeutic options for EHE are limited, including resection of primary and metastatic tumors, organ transplantation and rather ineffective systemic approaches. Driver mutations have been reported (fusion transcripts of either YAP-TFE3 or WWTR1-CAMTA1) but comprehensive molecular profiling has not been performed. Our aim was to molecularly characterize hepatic EHE to identify new molecular targets. Eight primary hepatic EHE were analyzed by next-generation sequencing using a 409-gene panel. The majority of primary hepatic EHE revealed a low number of mutations. Genes that were mutated primarily are involved in DNA repair, epigenetic regulation, signaling pathways and cell cycle control, indicating that EHE present with mutations in various functions. Although only detecting a low mutation rate, a comparison with comprehensive databases (target db V3) revealed mutations in five genes with putative therapeutical options. Therefore, our findings help to shed light on the molecular background of EHE and might pave the way to new therapeutic approaches.