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

iScience (Oct 2024)

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

Journal volume & issue: Vol. 27, no. 10
p. 110862

Abstract

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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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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