title: Successful establishment of patient-derived tumor xenografts from gastrointestinal stromal tumor-a single center experience.
abstract: Patient-derived tumor xenografts (PDTX) generally represent a kind of more reliable model of human disease, by which a potential drugs' preclinical efficacy could be evaluated. To date, no stable gastrointestinal stromal tumor (GIST) PDTX models have been reported. In this study, we aimed to establish stable GIST PDTX models and to evaluate whether these models accurately reflected the histological feature of the corresponding patient tumors and create a reliable GIST PDTX models for our future experiment. By engrafting fresh patient GIST tissues into immune-compromised mice (BALB/c athymic mice), 4 PDTX models were established. Histological features were assessed by a qualified pathologist based on H&E staining, CD117 and DOG-1. We also conduct whole exome sequencing(WES) for the 4 established GIST PDTX models to test if the model still harbored the same mutation detected in corresponding patient tumors and get a more intensive vision for the genetic profile of the models we have established, which will help a lot for our future experiment. To explore the tumorigenesis mechanism for GIST, we also have a statistical analysis for the genes detected as nonsynchronous-mutated simultaneously in 4 samples. All 4 GIST PDTX models retained the histological features of the corresponding human tumors, with original morphology type and positive stains for CD117 and DOG-1. Between the GIST PDTX models and their parental tumors, a same mutation site was detected, which confirmed the genetic consistency. The stability of molecular profiles observed within the GIST PDTX models provides confidence in the utility and translational significance of these models for in vivo testing of personalized therapies. To date, we conducted the first study to successfully establish a GIST PDTX model whose genetic profiles were revealed by whole exome sequencing. Our experience could be of great use.
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University Shanghai 200032, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University Shanghai 200032, China.
authors.forename: Han-Xing
authors.initials: HX
authors.lastname: Tong
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University Shanghai 200032, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Zhongshan Hospital, Fudan University Shanghai 200032, China.
authors.forename: Ying-Yong
authors.initials: YY
authors.lastname: Hou
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University Shanghai 200032, China.
authors.forename: Jing-Lei
authors.initials: JL
authors.lastname: Li
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University Shanghai 200032, China.
authors.forename: Jiong-Yuan
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Department of Oncology, Zhongshan Hospital, Fudan University Shanghai 200032, China.
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University Shanghai 200032, China.
authors.forename: Wei-Qi
authors.initials: WQ
authors.lastname: Lu
keywords: Patient-derived tumor xenografts; gastrointestinal stromal tumor; whole exome sequencing