{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE293nnn/GSE293764/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Other"],"species":["Homo sapiens"],"gds_type":["Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE293764"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Decrypting Oncogenic Circuitry Through Translocation-Induced Enhancer Hijacking by TransFinder [Hi-C]","description":"While IGH enhancer translocations are well-established drivers of multiple myeloma (MM), routine diagnostics detect these events in only 32~38% of patients. Here we introduce TransFinder, a multi-omics pipeline integrating SMRT-seq, Hi-C, RNA-seq, and CUT&Tag to systematically resolve cryptic translocations and their hijacked oncogenes by deconvoluting enhancer-promoter neo-loops at rearrangement breakpoints. Applied to MM, TransFinder identified that t(16;22)(q23;q11), a canonical translocation known to activate MAF, also hijacks enhancers to activate RAB36. It further uncovered previously unrecognized translocations, t(5;8)(q35;q24) and t(1;22)(q25;q13), that activate MYC and CBX7 transcription, respectively, through chromatin topology rewiring. CRISPR-Cas9-engineered t(1;22)(q25;q13) recapitulated CBX7 induction, and pharmacological inhibition of CBX7 suppressed myeloma cell proliferation. Beyond MM, TransFinder identified enhancer-hijacking events in other malignancies, including chronic myeloid leukemia (CML), where t(9;22)(q34;q11) repositioned an enhancer to activate BCR-ABL1 transcription, and pancreatic ductal adenocarcinoma (PDAC), where t(2;12)(p24;q24) hijacked an enhancer to ectopically activate SDC1. By bridging 3D genome architecture with oncogene activation, TransFinder decodes oncogenic structural variants and their trans-activities, establishing clinically actionable dependencies of non-coding drivers in malignancies with complex karyotypic alterations.","dates":{"publication":"2026/09/03"},"accession":"GSE293764","cross_references":{"GSM":["GSM8889678","GSM8889677","GSM8889679","GSM8889674","GSM8889673","GSM8889676","GSM8889675","GSM8889672","GSM8889671"],"GPL":["29480"],"GSE":["293764"],"taxon":["Homo sapiens"]}}