Recent progress in the genomics of soft tissue sarcomas

Soft tissue sarcomas represent a diverse group of tumors with unique clinical features and genetic aberrations; because of their biological characteristics and rarity, advances in diagnostic measures and therapeutic interventions have been slow. Genomic analysis provides a means to elucidate new gene signatures or pathways for possible therapeutic manipulation, predictors of prognosis, and improved diagnostic classification.

Genomic profiling of soft tissue sarcomas subtypes reveals a propensity for tumors of less karyotypic diversity to segregate from the more pleomorphic subtypes. Certain statistical methods such as support vector machine analysis can distinguish pleomorphic subgroups such as malignant fibrous histiocytomas from other sarcomas. Genomic approaches have led to the identification of several pathways of interest, including the retinoic acid pathway, as well as multiple receptor tyrosine kinases such as platelet-derived growth factor receptor, vascular endothelial growth factor receptor, and epidermal growth factor receptor. Genomic analysis of Ewing's sarcoma identified a limited set of genes that can detect subclinical disease with prognostic implications. Finally, a novel paired gene analysis was shown to distinguish gastrointestinal stromal tumor from leiomyosarcoma with high sensitivity and specificity.

A functional genomic approach to sarcoma can elucidate new diagnostic techniques, highly sensitive biomarkers for detection of minimal residual disease, and prognostic tools. Ultimately, these genomic approaches may improve upon the current standards of care for patients afflicted with sarcoma.