Figure 1.

Genomic changes in soft-tissue sarcoma.

Notes: Liposarcomas consist of four subtypes: well-differentiated liposarcoma (WDLS), dedifferentiated liposarcoma, myxoid liposarcoma (MLS), and pleomorphic liposarcoma (PLS). A common characteristic of WDLS, DDLS, and PLS is amplifications in HMGA2, MDM2, and CDK4. PLS bears additional CCND1 amplifications. MLS, on the other hand, harbors a fusion of TLS/FUS–CHOP, which is responsible for pathogenesis. Angiosarcomas are diverse malignancies and bear aberrations in MYC, VEGF/VEGFR, PTPRB, and PLCG1. Leiomyosarcomas have frequent X-chromosome (Chr) gains, constitutively activated Akt and losses in Chr 10, which bears the PTEN gene. The two latter aberrations lead to mTOR activation via TSC2 and are instrumental in disease pathology. Rhabdomyosarcoma can be subtyped into alveolar rhabdomyosarcoma (ARMS) and embryonic rhabdomyosarcoma (ERMS). The former is associated with PAX3/7–FOXO1 fusions and cause Hippo-pathway dysregulation accompanied by bypass of cellular senescence, and the latter is distinguished by losses in Chr 11, along with gene mutations in the Ras pathway. Other pathways involved include Hedgehog, PI3K, and p53. Ewing’s sarcoma is characterized by EWS–ETS gene fusion, and this potent transcription factor induces genes associated with proliferation, apoptosis inhibition, and metabolic changes to favor biosynthesis and cell division. Synovial sarcoma (SS) is associated with SYT–SSX fusions: SYT–SSX2 for monophasic SS and SYT–SSX1/2 for biphasic SS. Arrows indicate gene transcription.