Patient-derived rhabdomyosarcoma cells recapitulate the genetic and transcriptomic landscapes of primary tumors
Yuxiang Hu,
Ziqi He,
Shuangai Liu,
Wenwen Ying,
Yifan Chen,
Manli Zhao,
Min He,
Xuan Wu,
Yinbing Tang,
Weizhong Gu,
Meidan Ying,
Jinhu Wang,
Ting Tao
Affiliations
Yuxiang Hu
Pediatric Cancer Research Center, National Clinical Research Center for Child Health, Hangzhou 310052, China; Department of Surgical Oncology, Children’s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China; The First Clinical Institute, Zunyi Medical University, Zunyi 563000, China
Ziqi He
Pediatric Cancer Research Center, National Clinical Research Center for Child Health, Hangzhou 310052, China; Department of Surgical Oncology, Children’s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China; The First Clinical Institute, Zunyi Medical University, Zunyi 563000, China
Shuangai Liu
Pediatric Cancer Research Center, National Clinical Research Center for Child Health, Hangzhou 310052, China; Department of Surgical Oncology, Children’s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China; The First Clinical Institute, Zunyi Medical University, Zunyi 563000, China
Wenwen Ying
Institute of Pharmacology and Toxicology, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
Yifan Chen
Institute of Pharmacology and Toxicology, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
Manli Zhao
Department of Pathology, Children’s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China
Min He
Pediatric Cancer Research Center, National Clinical Research Center for Child Health, Hangzhou 310052, China; Department of Surgical Oncology, Children’s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China
Xuan Wu
Pediatric Cancer Research Center, National Clinical Research Center for Child Health, Hangzhou 310052, China; Department of Surgical Oncology, Children’s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China
Yinbing Tang
Pediatric Cancer Research Center, National Clinical Research Center for Child Health, Hangzhou 310052, China; Department of Surgical Oncology, Children’s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China
Weizhong Gu
Department of Pathology, Children’s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China
Meidan Ying
Pediatric Cancer Research Center, National Clinical Research Center for Child Health, Hangzhou 310052, China; Institute of Pharmacology and Toxicology, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Cancer Center, Zhejiang University, Hangzhou 310058, China; Corresponding author
Jinhu Wang
Pediatric Cancer Research Center, National Clinical Research Center for Child Health, Hangzhou 310052, China; Department of Surgical Oncology, Children’s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China; Key Laboratory of Diagnosis and Treatment of Neonatal Diseases of Zhejiang Province, Hangzhou 310052, China; Cancer Center, Zhejiang University, Hangzhou 310058, China; Corresponding author
Ting Tao
Pediatric Cancer Research Center, National Clinical Research Center for Child Health, Hangzhou 310052, China; Department of Surgical Oncology, Children’s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China; Key Laboratory of Diagnosis and Treatment of Neonatal Diseases of Zhejiang Province, Hangzhou 310052, China; Cancer Center, Zhejiang University, Hangzhou 310058, China; Corresponding author
Summary: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in childhood and adolescence. The availability of appropriate and well-characterized preclinical models for RMS is limited, posing a challenge for investigating the molecular mechanisms and evaluating new targeted compounds in preclinical settings. Here, we collected 51 RMS specimens (referred to as ZJUCH-RMS cohort) and established 9 patient-derived cells (PDCs) and validated the identity of these cells by the expression of RMS-specific markers. Whole-transcriptome analysis identified high-confidence mutations in ZJUCH-RMS cohort including RAS, TP53, ARID1A, MYOD1, and MYCN. Further studies showed that RMS PDCs retained the genetic alterations and the expression of RMS hallmark and dependency genes in matched primary tumors and acted as valuable tools to assess drug responses and pharmacogenomic interactions. Our study provides unique PDCs that are available for preclinical studies of RMS and further advances the feasibility of RMS PDCs as valuable tools for developing personalized treatments for patients.
