{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE292nnn/GSE292882/"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"omics_type":["Other"],"species":[" Homo sapiens","unidentified"],"gds_type":["Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE292882"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"FANCM is Required for the PAX3::FOXO1-Driven Oncogenic Program in Rhabdomyosarcoma [CRISPR Screen]","description":"Alveolar rhabdomyosarcoma (ARMS) is a highly aggressive pediatric soft tissue sarcoma driven by the PAX3::FOXO1 fusion protein. Despite multipronged treatment approaches, survival rates for patients with fusion-positive (FP) ARMS remain poor, underscoring the need for novel therapeutic strategies. Here, we employ sequential multimodal CRISPR/Cas9 genetic screens to identify essential genes in FP ARMS, revealing FANCM, a key component of the Fanconi Anemia pathway, as a critical dependency. FANCM loss selectively impairs FP ARMS cell growth in vitro and in vivo, reduces PAX3::FOXO1 levels, and induces myogenic differentiation. Mechanistically, FANCM depletion exacerbates replication stress, particularly at PAX3::FOXO1 target gene loci, which leads to ATR/ATM-mediated DNA damage signaling and selective downregulation of the fusion-driven oncogenic program. CRISPR exon-tiling screens highlighted FANCM's helicase and DNA-binding domains as essential for its FP-specific dependency, linking FANCM-mediated replication fork binding and downstream ATR signaling to FP ARMS survival. This study positions FANCM as a promising therapeutic target in FP ARMS and introduces a novel paradigm for exploiting replication stress vulnerabilities in oncofusion-driven malignancies.","dates":{"publication":"2026/08/04"},"accession":"GSE292882","cross_references":{"GSM":["GSM8868010","GSM8868011","GSM8868012","GSM8868013","GSM8868014","GSM8868015","GSM8868016","GSM8868017","GSM8868018","GSM8868019","GSM8868020","GSM8868021","GSM8868022","GSM8868023","GSM8868024","GSM8868025","GSM8868026","GSM8868027","GSM8868028","GSM8868029","GSM8868030","GSM8867980","GSM8867989","GSM8867981","GSM8867982","GSM8867983","GSM8867984","GSM8867985","GSM8867986","GSM8867987","GSM8867988","GSM8868000","GSM8868001","GSM8867990","GSM8867991","GSM8868002","GSM8868003","GSM8867992","GSM8868004","GSM8867993","GSM8867994","GSM8868005","GSM8868006","GSM8867995","GSM8868007","GSM8867996","GSM8867997","GSM8868008","GSM8868009","GSM8867998","GSM8867999"],"GPL":["30882","32371","24676"],"GSE":["292882"],"taxon":[" Homo sapiens","unidentified"]}}