Genetic abnormalities in soft tissue sarcomas - Implications for treatment

PURPOSE OF REVIEW: After reading this article the reader should have a conceptual understanding of the molecular biology of soft tissue sarcomas. RECENT FINDINGS: Five broad categories of oncogenes have been described: (1) growth factor receptors, (2) signal transducers, (3) nuclear oncoproteins, (4) antagonists of apoptosis and (5) antagonists of tumor suppressors. SUMMARY: Some of the more important oncogenes include ras, myc, src, Her-2/neu (also called erbB-2), hTERT and Bcl-2. The p53 protein is essential for the checkpoint control that arrests human cells with damaged DNA in G1. Replication of such cells would tend to perpetuate mutations. TP53 functions as a transcription factor to induce expression of p21, an inhibitor of G1 Cdk-cyclin complexes. Mutations in the p53 gene occur in more than 50% of human cancers. As p53 is a tetramer, a point mutation in one p53 allele can be sufficient to inhibit all p53 activity. MDM2, a protein that normally inhibits the ability of p53 to restrain the cell cycle or kill the cell, is overexpressed in several cancers. Defects in cellular DNA repair processes found in certain human diseases are associated with an increased susceptibility for certain cancers, including soft tissue sarcomas.