Patrick P. Lin, M.D.
Present Title & Affiliation
Associate Professor, Department of Orthopedic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
- Mouse models of Ewing’s sarcoma and osteosarcoma
Ewing’s sarcoma is the second most common bone malignancy that affects children and adolescents. The poorly differentiated tumors are aggressive and metastasize early to lung, bone marrow and other tissues. In all cases of the disease, there is a characteristic reciprocal chromosomal translocation, which leads to an in-frame fusion between the EWS gene and one of the ETS family gene members. In approximately 85% of cases, the EWS gene is combined with the ETS gene FLI1 in a t(11;22) translocation.
Our laboratory is focused upon understanding the role EWS-FLI1 plays in the development of Ewing’s sarcoma. To this end we have created a unique mouse model involving conditional expression of EWS-FLI1. Our previous research suggested that cooperating mutations are necessary for EWS-FLI1 to be transformed in vivo. While p53 and Arf can cooperate with EWS-FLI1 to generate tumors in mice, clinical data from patients seem to indicate that this is not likely to be the primary genetic pathway for the tumor to form. Therefore, our current efforts are geared toward developing an unbiased genetic screen of potentially cooperative mutations in our mouse model.
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