phs001982
Copy Number Alteration Profiling of Myxofibrosarcoma and Undifferentiated Pleomorphic Sarcoma
Myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) are highly genetically complex soft tissue sarcomas. Up to 50% of patients develop distant metastases, but current systemic therapies have limited efficacy. MFS and UPS have recently been shown to commonly harbor copy number alterations or mutations in the tumor suppressor genes RB1 and TP53. As these alterations have been shown to engender dependence on the oncogenic protein Skp2 for survival of transformed cells in mouse models, we sought to examine its function and potential as a therapeutic target in MFS/UPS. Comparative genomic hybridization (CGH) and next-generation sequencing (NGS) confirmed that a significant fraction of MFS and UPS patient samples (n=94) harbor chromosomal deletions and/or loss-of-function mutations in RB1and TP53(88% carry alterations in at least one gene; 60% carry alterations in both). Tissue microarray (TMA) analysis identified a correlation between absent... (for more see dbGaP study page.)