Establishing a patient-derived xenograft model of human myxoid and round-cell liposarcoma
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Yiming Qi1,*, Yu Hu1,*, Hua Yang2,*, Rongyuan Zhuang3,*, Yingyong Hou4, Hanxing Tong2, Yi Feng3, Yuan Huang5, Quan Jiang2, Qunsheng Ji6, Qingyang Gu6, Zhixiang Zhang6, Xuzhen Tang6, Weiqi Lu2 and Yuhong Zhou3
1Departments of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai, China
2Departments of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
3Departments of Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
4Departments of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
5Endoscopy Center, Zhongshan Hospital, Fudan University, Shanghai, China
6Oncology BU, Research Service Division, WuXi AppTec, Shanghai, China
*These authors contributed equally to this work
Yuhong Zhou, email: firstname.lastname@example.org
Weiqi Lu, email: email@example.com
Keywords: liposarcoma, MRCL, PDX model, PIK3CA mutation, PI3K/mTOR pathway
Received: September 18, 2016 Accepted: April 10, 2017 Published: April 21, 2017
Myxoid and round cell liposarcoma (MRCL) is a common type of soft tissue sarcoma. The lack of patient-derived tumor xenograft models that are highly consistent with human tumors has limited the drug experiments for this disease. Hence, we aimed to develop and validate a patient-derived tumor xenograft model of MRCL. A tumor sample from a patient with MRCL was implanted subcutaneously in an immunodeficient mouse shortly after resection to establish a patient-derived tumor xenograft model. After the tumor grew, it was resected and divided into several pieces for re-implantation and tumor passage. After passage 1, 3, and 5 (i.e. P1, P3, and P5, respectively), tumor morphology and the presence of the FUS-DDIT3 gene fusion were consistent with those of the original patient tumor. Short tandem repeat analysis demonstrated consistency from P1 to P5. Whole exome sequencing also showed that P5 tumors harbored many of the same gene mutations present in the original patient tumor, one of which was a PIK3CA mutation. PF-04691502 significantly inhibited tumor growth in P5 models (tumor volumes of 492.62 ± 652.80 vs 3303.81 ± 1480.79 mm3, P < 0.001, in treated vs control tumors, respectively) after 29 days of treatment. In conclusion, we have successfully established the first patient-derived xenograft model of MRCL. In addition to surgery, PI3K/mTOR inhibitors could potentially be used for the treatment of PIK3CA-positive MRCLs.
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