Human Sarcomas

Cell Transformation Team

Section: Section of Molecular Carcinogenesis

Soft tissue tumours are a heterogeneous group of mesenchymal tumours that arise as soft tissue masses and that frequently exhibit the differentiated features of adult soft tissue. Major histologic categories of malignant soft tissue sarcomas include leiomyosarcoma (smooth muscle), rhabdomyosarcoma (striated muscle), liposarcoma (fatty tissue), synovial sarcoma, and malignant fibrous histiocytoma. The disease accounts for ~1% of all cancers and is associated with a substantial mortality rate of ~50%, which is related in part to its propensity for metastasis. The clinical behaviour of soft tissue sarcomas is highly variable, but few reliable determinants of outcome have been identified. New markers that predict clinical outcome, in particular the propensity of primary tumours to develop metastatic tumours, are urgently needed and would be of great clinical use, allowing for more selective treatment strategies. 

A gene expression signature associated with metastatic outcome in human leiomyosarcomas

Investigators; YF Lee, A Falconer, S Edwards, J Clark, P Flohr, T Roe, R Wang, J Shipley, C Fisher, I Judson, CS Cooper

External Funding: Cancer Research UK

Metastasis is a major factor associated with poor prognosis in cancer, but little is know of its molecular mechanisms. Although the clinical behaviour of soft tissue sarcomas is highly variable, few reliable determinants of outcome have been identified. New markers that predict clinical outcome, in particular the ability of primary tumours to develop metastatic tumours, are urgently needed. We have chosen leiomyosarcoma as a model for examining the relationship between gene expression profile and the development of metastasis in soft tissue sarcomas. Using cDNA microarray, we identified a gene expression signature associated with metastasis in sarcoma that allowed prediction of the future development of metastases of primary tumours (Kaplan-Meier analysis P=0.001). Our finding may aid the tailoring of therapy for individual sarcoma patients, where the aggressiveness of treatment is affected by the predicted outcome of disease.