Genetic and molecular abnormalities in tumors of the bone and soft tissues

Background: Malignant transformation requires the accumulation of multiple genetic alterations such as chromosomal abnormalities, oncogene activation, loss of tumor suppressor genes, or abnormalities in genes that control DNA repair and genomic instability. Sarcomas are a heterogeneous group of malignant mesenchymal tumors of difficult histologic classification and strong genetic predisposition. This article provides a comprehensive review of the cytogenetic abnormalities observed in bone and soft-tissue tumors, emphasizing known downstream molecular changes that may play a role in oncogenesis.

Methods: The database of the National Library of Medicine was searched for literature relating to genetic and molecular mechanisms in sarcomas in general and in each of the main tumor entities.

Results: Recent techniques in chromosome analysis and molecular cytogenetics have improved our ability to characterize genetic changes in mesenchymal tumors. Some changes are so characteristic as to be virtually pathognomonic of particular histologic types, while Others are complex, difficult to characterize, and of unknown relevance to pathogenesis. The implications to the cell of some of these abnormalities are now being recognized.

Conclusions: The study of sarcomas will benefit from the information derived from genetic studies and translational research. The human genome project and new methodologies, such as computer-based DNA microarray, may help in the histogenetic classification of sarcomas and in the identification of molecular targets for therapy.