Genetic Screen in a Preclinical Model of Sarcoma Development Defines Drivers and Therapeutic Vulnerabilities.

ABSTRACT:

Purpose

High-grade complex karyotype sarcomas are a heterogeneous group of tumors with a uniformly poor prognosis. Within complex karyotype sarcomas, there are innumerable genetic changes but identifying those that are clinically relevant has been challenging.

Experimental design

To address this, we utilized a pooled genetic screening approach, informed by The Cancer Genome Atlas (TCGA) data, to identify key drivers and modifiers of sarcoma development that were validated in vivo.

Results

YAP1 and wild-type KRAS were validated as drivers and transformed human mesenchymal stem cells into two distinct sarcoma subtypes, undifferentiated pleomorphic sarcoma and myxofibrosarcoma, respectively. A subset of tumors driven by CDK4 and PIK3CA reflected leiomyosarcoma and osteos

SUBMITTER: Freeland J 

PROVIDER: S-EPMC11530313 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature