{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE292nnn/GSE292876/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Homo sapiens"],"gds_type":["Genome binding/occupancy profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE292876"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"FANCM is Required for the PAX3::FOXO1-Driven Oncogenic Program in Rhabdomyosarcoma [ChIP-Seq]","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":"GSE292876","cross_references":{"GSM":["GSM8867846","GSM8867847","GSM8867848","GSM8867849","GSM8867839","GSM8867850","GSM8867851","GSM8867840","GSM8867841","GSM8867852","GSM8867853","GSM8867842","GSM8867854","GSM8867843","GSM8867844","GSM8867855","GSM8867856","GSM8867845"],"GPL":["34284"],"GSE":["292876"],"taxon":["Homo sapiens"]}}