{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE328nnn/GSE328026/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328026"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"MiT Fusions, TSC1–TSC2 Divergence, and Stem-like Programs Reveal Distinct Origins and Vulnerabilities in PEComa [RNA-seq]","description":"Perivascular epithelioid cell neoplasms (PEComas) are ultra-rare mesenchymal tumors lacking a molecular classification to guide therapy. Here we perform comprehensive multi-omic profiling of an unselected PEComa cohort. We identify frequent MITF rearrangements involving actin gene partners (ACTA2, ACTG1 and ACTB). Anatomical stratification reveals cyclin-dependent kinase module mutations in gynecologic tumors, whereas soft tissue, gastrointestinal, and pelvic tumors lacked mTOR pathway alterations but are enriched for TFE3/MITF rearrangements. Transcriptomic analysis defines four subtypes with distinct lineage programs—melanocytic, mesenchymal, or adipogenic—as well as unique mutational patterns and clinical behaviors. Notably, an aggressive stem-like subtype enriched for TP53/RB1 mutations exhibits high proliferation, activation of embryonic and Hedgehog signaling, immune infiltration, and resistance to mTOR inhibitors, but potential responsiveness to immunotherapy. Single-nucleus RNA sequencing reveals intra-tumoral heterogeneity within this subtype, including divergent inflammatory states. Together, these findings establish a molecular classification framework and identify actionable vulnerabilities in PEComa.","dates":{"publication":"2026/04/18"},"accession":"GSE328026","cross_references":{"GSM":["GSM9670529","GSM9670528","GSM9670527","GSM9670526","GSM9670525","GSM9670524","GSM9670534","GSM9670533","GSM9670499","GSM9670532","GSM9670531","GSM9670498","GSM9670530","GSM9670497","GSM9670496","GSM9670495","GSM9670494","GSM9670493","GSM9670492","GSM9670491","GSM9670490","GSM9670539","GSM9670538","GSM9670537","GSM9670536","GSM9670535","GSM9670545","GSM9670501","GSM9670500","GSM9670544","GSM9670543","GSM9670542","GSM9670541","GSM9670540","GSM9670509","GSM9670508","GSM9670507","GSM9670506","GSM9670505","GSM9670549","GSM9670548","GSM9670504","GSM9670503","GSM9670547","GSM9670502","GSM9670546","GSM9670512","GSM9670511","GSM9670555","GSM9670510","GSM9670554","GSM9670553","GSM9670552","GSM9670551","GSM9670550","GSM9670519","GSM9670518","GSM9670517","GSM9670516","GSM9670515","GSM9670514","GSM9670513","GSM9670523","GSM9670522","GSM9670489","GSM9670488","GSM9670521","GSM9670520","GSM9670487"],"GPL":["20301","30173"],"GSE":["328026"],"taxon":["Homo sapiens"]}}