Genomically Complex Human Angiosarcoma and Canine Hemangiosarcoma Establish Convergent Angiogenic Transcriptional Programs

摘要: Sporadic angiosarcomas (ASs) are aggressive vascular sarcomas whose rarity and genomic complexity present significant obstacles in deciphering the pathogenic significance of individual genetic alterations. Numerous fusion genes have been identified across multiple types cancers, but their existence remain unclear sporadic ASs. In this study, we leveraged RNA sequencing data from thirteen human ASs 76 spontaneous canine hemangiosarcomas (HSAs) to identify associated with malignancies. Ten novel protein-coding genes, including TEX2-PECAM1 ATP8A2-FLT1, were seven tumors, two tumors showing mutations TP53. HRAS NRAS found without fusions or TP53 mutations. We fifteen MYO16-PTK2, GABRA3-FLT1, AKT3-XPNPEP1 eleven HSAs; these seen exclusively angiogenic molecular subtype that contained recurrent TP53, PIK3CA, PIK3R1, NRAS. particular, co-occurred higher frequency than expected by random chance, they enriched gene signatures predicting activation pathways. Comparative transcriptomic analysis HSAs shared PI3K/AKT/mTOR Our suggest instability induced might create a predisposition for events may contribute tumor progression promoting selection and/or enhancing fitness through convergent pathways malignancy.