Common Secondary Genomic Variants Associated With Advanced Epithelioid Hemangioendothelioma

Key Points Question Can next-generation sequencing reveal rationale for the dichotomous biological activity of epithelioid hemangioendothelioma (EHE) while illuminating potentially actionable alterations? Findings In a cross-sectional study of next-generation sequencing results collected from 49 participants diagnosed with EHE, more than half of patients with EHE profiled exhibited pathogenic genomic variants in addition to the WWTR1-CAMTA1 fusion, with 18.4% of participants exhibiting a potentially targetable variant. Participants with stage III/IV EHE were more likely to exhibit a secondary pathogenic variant. Meaning Next-generation sequencing may identify secondary genomic variants that are associated with EHE aggressiveness; additionally, these variants may represent potential therapeutic targets.