Sarcomas

Abstract

Oncologic molecular pathology focuses on identifying and understanding molecular and genetic alterations underlying the development and progression of neoplastic processes. Mesenchymal malignancies may be classified into two pathogenetic types: sarcomas with complex genetic alterations and sarcomas with specific recurrent chromosomal translocations. The first type includes the majority of high-grade, pleomorphic mesenchymal malignancies that are characterized by complex chromosomal abnormalities, for example, malignant fibrous histiocytoma (MFH), osteogenic sarcoma, and embryonal rhabdomyosarcoma. In the second type, the sarcomas are translocation specific, that is, harboring a recurrent chromosomal translocation leading to an in-frame fusion of coding sequences from each of the two rearranged genes. The translocation results in the production of a chimeric transcript encoding a fusion protein with oncogenic activity. Histologically, the translocation-specific sarcomas are generally a monomorphic proliferation of neoplastic cells. This pathogenetic classification appears biologically relevant and is best illustrated by the sarcoma types observed in Li-Fraumeni syndrome and therapy-related malignancies. © 2007 Springer Science+Business Media, LLC.