Gene Fusions Encoding Chimaeric Transcription Factors in Solid Tumours

Analysis of chromosomal alterations in human malignancies has revealed recurring genetic changes that are often closely associated with specific subtypes of tumours. Among solid tumours, cytogenetic analysis of a group of primitive sarcomas occurring principally in children and young adults has identified specific non-random chromosomal translocations associated with these malignancies. A number of the translocation breakpoints have now been cloned, revealing the in frame fusion of genes located at each partner breakpoint. The common theme is the expression by these hybrid genes of chimaeric proteins containing functional domains from each fusion partner. These domains confer transcriptional activation or repression, DNA binding specificity, or other novel protein-protein interactions. The net result appears to be the expression of chimaeric oncoproteins that function in transformation by dysregulating gene transcription.