MM samples for epigenomic translocation of H3K4me3 broad domains following super-enhancer hijacking
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ABSTRACT:
PROVIDER: EGAS00001005684 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Chromosomal translocations are important drivers of haematological malignancies whereby proto-oncogenes are activated by juxtaposition with super-enhancers, often called super-enhancer hijacking. We analysed the epigenomic consequences of rearrangements between the enhancers of the immunoglobulin heavy chain locus (IGH) and proto-oncogene CCND1 that are common in B-cell malignancies. By integrating BLUEPRINT epigenomic data with DNA breakpoint detection, we characterised the normal chromatin landscape of the human IGH locus and its dynamics after pathological genomic rearrangement. We detected an H3K4me3 broad domain (BD) within the IGH locus of healthy B-cells that was absent in samples with IGH-CCND1 translocations. The appearance of H3K4me3-BD over CCND1 in the latter was associated with overexpression and extensive chromatin accessibility of this locus. We observed similar cancer-specific H3K4me3-BDs associated with super-enhancer hijacking of other common oncogenes in B-cell (MAF, MYC and FGFR3) and in T-cell malignancies (LMO2, TLX3 and TAL1). Our analysis suggests that H3K4me3-BDs are created by super-enhancers and supports the new concept of epigenomic translocation, where the relocation of H3K4me3-BDs accompanies the translocation of super-enhancers.
2020-08-12 | GSE151556 | GEO
Project description:Epigenomic translocation of H3K4me3 broad domains following super-enhancer hijacking
| PRJNA636364 | ENA
Project description: Not available
| S-EPMC9341503 | biostudies-literature
Project 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.
2026-09-03 | GSE293764 | GEO
Project 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.
2026-09-03 | GSE294550 | GEO
Project 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.
2026-09-03 | GSE293724 | GEO
Project 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.
2026-09-03 | GSE293723 | GEO
Project 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.
2026-09-03 | GSE293721 | GEO
Project 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.
2026-09-03 | GSE293747 | GEO
Project 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.
2026-09-03 | GSE293726 | GEO