Molecular biology of sarcomas

There are two types of sarcomas with regards to the type of molecular alterations: sarcomas with relatively simple, usually specific lesions and those with complex unspecific lesions. A molecular classification for sarcomas can therefore be proposed (Table 1). Recurrent chromosomal translocations: about 10-15% of all sarcomas bear a recurrent chromosomal translocation (Table 2). The most frequent sarcomas with such an abnormality are dermatofibrosarcoma protuberans (DFSP), myxoid liposarcoma, Ewing’s sarcoma, and synovial sarcoma. Each of these translocations generates a fusion gene believed to be directly related to the pathogenesis of the sarcoma in which it is expressed1,2 (Fig. 1). Most of these gene fusions encode aberrant chimeric transcription factors by combining a strong promoter (e.g. EWSR1), which confers the expression level, and a DNA-binding domain (e.g. FLI1, ERG, ATF1, WT1), which confers the target specificity of the transcriptional activation. A second mechanism describes results in an autocrine growth factor, as seen in DFSP and giant cell fibroblastoma with COL1A-PDGFB gene fusion. This fusion puts platelet-derived growth factor receptor beta (PDGFRB) under the control of the COL1A1 promoter, thus Molecular biology of sarcomas