The Cancer Genome Atlas Impact and Future Directions in Sarcoma

TCGA initiative and related studies serve an invaluable role in laying a foundational understanding of the genomic landscape of sarcoma, upon which future advances in clinical management will be built. TCGA demonstrates that copy number alterations of key regulatory genes (TP53, RB1) are heavily involved in the 5 complex-genome sarcomas surveyed (DDLPS, LMS, UPS, MFS, and MPNST); this contrasts with SS, the single simple karyotype, translocation-driven sarcoma evaluated by TCGA. Novel molecular mechanisms and targets were not identified through TCGA assessment, but genomic markers of prognosis, such as methylation patterns, and the influence of the immune microenvironment were described. Classification of STS by gene expression signature has an increasingly important role in the clinical domain by imparting a more accurate prognostic picture and by influencing clinical trial design. Sarcoma remains a devastating clinical condition, and although considerable advances have been made in understanding the molecular basis of sarcoma pathophysiology, additional diagnostic and therapeutic challenges remain. Further understanding of the genetic and immunologic features of sarcoma genesis is vital for directing future research endeavors, which are hoped to lead to clinically applicable insights that may lessen the impact of sarcoma on patients diagnosed with this rare group of malignancies.