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iScience

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Patient-derived rhabdomyosarcoma cells recapitulate the genetic and transcriptomic landscapes of primary tumors

Published:31 August 2024 DOI: 10.1016/j.isci.2024.110862
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

Abstract

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.

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