Soft tissue tumours: the genetic basis of development.

Introduction The term soft tissue tumours is used to describe a heterogeneous group of neoplasms that exhibit the differentiated features of various supporting tissues of the body, such as smooth and striated muscle, fat, fibrous tissue and vessels (1). Together with tumours of bone, they form a major histogenetic class distinct from neoplasms of epithelial origin (adenomas and carcinomas), blood and lymphoreticular origin (leukaemias and lymphomas) and of the central nervous system. They are usually named according to the tissue they most resemble, though in some cases, such as synovial sarcoma, there is no clear normal tissue homologue (Table I). Malignant soft tissue tumours (sarcomas) account for ~ 1 % of human malignancies and ~2% of cancer deaths. They include liposarcoma (fat), leiomyosarcoma (smooth muscle), angiosarcoma (vessels), rhabdomyosarcoma (striated muscle) and the commonest form, malignant fibrous histiocytoma. By convention, peripheral nerve sheath tumours are also included. Sarcomas are relatively more common in children, with rhabdomyosarcoma accounting for 6 -7% of childhood cancers. Benign soft tissue tumours are at least 100 times more common than their malignant counterparts and include some of die commonest types of human neoplasm. Although non-invasive and usually not life threatening, some benign lesions, e.g. leiomyomas of the uterus, are associated with considerable morbidity and commonly require surgical intervention. Until recently there has been relatively little interest in the molecular mechanisms underlying the development of human soft tissue tumours. This is somewhat ironic, since studies on the induction of soft tissue sarcomas in animal models and on the transformation of fibroblasts in vitro have provided many of the major conceptual advances in our understanding of malignant transformation. These include the notion that immortalization and transformation can represent different steps along the pathway to malignant conversion (2), the detection of many retroviral oncogenes, the development of assays for detecting activated oncogenes in human tumours (see below) and the original identification of the p53 tumour suppressor protein (3). However, considerable progress has recently been made in the form of cytogenetic analyses that have demonstrated the presence of specific chromosomal translocations in certain soft tissue tumours and by reports of alterations in dominant oncogenes and tumour suppressor genes. It is also well established that certain inherited disorders can predispose to the development of soft tissue