{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE328nnn/GSE328029/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Methylation profiling"],"species":["Homo sapiens"],"gds_type":["Methylation profiling by genome tiling array"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328029"],"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 [Methylation]","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":"GSE328029","cross_references":{"GSM":["GSM9670609","GSM9670608","GSM9670629","GSM9670607","GSM9670606","GSM9670628","GSM9670627","GSM9670605","GSM9670626","GSM9670604","GSM9670603","GSM9670625","GSM9670624","GSM9670602","GSM9670623","GSM9670601","GSM9670611","GSM9670633","GSM9670632","GSM9670610","GSM9670599","GSM9670631","GSM9670598","GSM9670597","GSM9670630","GSM9670596","GSM9670595","GSM9670594","GSM9670593","GSM9670592","GSM9670591","GSM9670590","GSM9670619","GSM9670618","GSM9670617","GSM9670616","GSM9670615","GSM9670614","GSM9670613","GSM9670612","GSM9670600","GSM9670589","GSM9670622","GSM9670588","GSM9670621","GSM9670620"],"GPL":["21145"],"GSE":["328029"],"taxon":["Homo sapiens"]}}