Oncotarget

Research Papers:

Establishing a patient-derived xenograft model of human myxoid and round-cell liposarcoma

Yiming Qi, Yu Hu, Hua Yang, Rongyuan Zhuang, Yingyong Hou, Hanxing Tong, Yi Feng, Yuan Huang, Quan Jiang, Qunsheng Ji, Qingyang Gu, Zhixiang Zhang, Xuzhen Tang, Weiqi Lu and Yuhong Zhou _

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Oncotarget. 2017; 8:54320-54330. https://doi.org/10.18632/oncotarget.17352

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Abstract

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

Correspondence to:

Yuhong Zhou, email: zhou.yuhong@zs-hospital.sh.cn

Weiqi Lu, email: lu.weiqi@zs-hospital.sh.cn

Keywords: liposarcoma, MRCL, PDX model, PIK3CA mutation, PI3K/mTOR pathway

Received: September 18, 2016     Accepted: April 10, 2017     Published: April 21, 2017

ABSTRACT

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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