Novel dedifferentiated liposarcoma xenograft models reveal PTEN down-regulation as a malignant signature and response to PI3K pathway inhibition.

[dedifferentiated liposarcoma]

Liposarcoma is a type of soft tissue sarcoma that exhibits poor survival and a high recurrence rate . Treatment is generally limited to surgery and radiation , which emphasizes the need for better understanding of this disease . Because very few in vivo and in vitro models can reproducibly recapitulate the human disease , we generated several xenograft models from surgically resected human dedifferentiated liposarcoma . All xenografts recapitulated morphological and gene expression characteristics of the patient tumors after continuous in vivo passages . Importantly , xenograftability was directly correlated with disease-specific survival of liposarcoma patients . Thus , the ability for the tumor of a patient to engraft may help identify those patients who will benefit from more aggressive treatment regimens . Gene expression analyses highlighted the association between xenograftability and a unique gene expression signature , including down-regulated PTEN tumor -suppressor gene expression and a progenitor-like phenotype . When treated with the PI 3 K /AKT /mTOR pathway inhibitor rapamycin alone or in combination with the multikinase inhibitor sorafenib , all xenografts responded with increased lipid content and a more differentiated gene expression profile . These human xenograft models may facilitate liposarcoma research and accelerate the generation of readily translatable preclinical data that could ultimately influence patient care .