Associate Research Fellow , National Taiwan University Hospital

Rare cancers pose significant challenges due to their heterogeneity and limited treatment options. In this talk, I will present integrative multiomics analyses of two rare vascular sarcomas: angiosarcoma and epithelioid hemangioendothelioma (EHE).

Liver angiosarcoma, more prevalent in Taiwan, was compared to non-liver cases using whole-exome and transcriptome sequencing. A dominant mutational signature linked to aristolochic acid exposure was identified exclusively in liver tumors. These tumors also showed elevated mutation burden, TP53/ATRX mutations, enhanced immune infiltration, and evidence of alternative lengthening of telomeres (ALT) without telomerase activity, revealing unique molecular features and potential therapeutic vulnerabilities.

For EHE, spatial transcriptomics using Visium CytAssist and Xenium platforms was applied to FFPE samples from eight patients across multiple organs. Unsupervised clustering identified both common and organ-specific tumor cell populations. Common clusters were enriched for stem-like endothelial markers and TGF-β/mTORC1 pathway activity, potentially explaining responses to sirolimus. Organ-specific clusters, especially in the liver, exhibited mesenchymal differentiation and high GDF-15 expression, linked to immune suppression and tumor aggressiveness.

These findings highlight distinct molecular and spatial features in rare vascular tumors, emphasizing the importance of integrative multiomics in uncovering shared mechanisms and guiding personalized therapeutic strategies.