FUS (16p11) gene rearrangement

Myxoid liposarcomas (MLS) are accounting for about 30% of liposarcomas and represent approximately 10% of adult soft tissue sarcomas. Patients with MLS showing progression to round-cell morphology have an inferior outcome. The most common aberration in MLS is the translocation t(12;16)(q13;p11) with a frequency of about 95% and to a much lesser extend t(12;22)(q13;q12), in which FUS is not involved. These reciprocal translocations are resulting in the generation of FUS-DDIT3 and EWSR1-DDIT3 fusion genes, respectively. As FUS is also involved in the development of low-grade fibromyxoid sarcoma with the rearrangement t(7;16)(q33;p11), FUS rearrangements are not highly specific for the detection of MLS. Human models of sarcomagenesis suggest that the FUS-DDIT3 fusion gene impedes with adipogenic differentiation of mesenchymal stem cells and thereby contributes to the development of liposarcoma.