Chromatin-based, in cis and in trans regulatory rewiring underpins distinct oncogenic transcriptomes in multiple myeloma
Multiple myeloma is a genetically heterogeneous cancer of the bone marrow plasma cells (PC). Distinct myeloma transcriptome profiles are primarily driven by myeloma initiating events (MIE) and converge into a mutually exclusive overexpression of the CCND1 and CCND2 oncogenes. Here, with reference to...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Springer Nature
2021
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| _version_ | 1826304819278643200 |
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| author | Alvarez-Benayas, J Trasanidis, N Katsarou, A Ponnusamy, K Chaidos, A May, PC Xiao, X Bua, M Atta, M Roberts, IAG Auner, HW Hatjiharissi, E Papaioannou, M Caputo, VS Sudbery, IM Karadimitris, A |
| author_facet | Alvarez-Benayas, J Trasanidis, N Katsarou, A Ponnusamy, K Chaidos, A May, PC Xiao, X Bua, M Atta, M Roberts, IAG Auner, HW Hatjiharissi, E Papaioannou, M Caputo, VS Sudbery, IM Karadimitris, A |
| author_sort | Alvarez-Benayas, J |
| collection | OXFORD |
| description | Multiple myeloma is a genetically heterogeneous cancer of the bone marrow plasma cells (PC). Distinct myeloma transcriptome profiles are primarily driven by myeloma initiating events (MIE) and converge into a mutually exclusive overexpression of the CCND1 and CCND2 oncogenes. Here, with reference to their normal counterparts, we find that myeloma PC enhanced chromatin accessibility combined with paired transcriptome profiling can classify MIE-defined genetic subgroups. Across and within different MM genetic subgroups, we ascribe regulation of genes and pathways critical for myeloma biology to unique or shared, developmentally activated or de novo formed candidate enhancers. Such enhancers co-opt recruitment of existing transcription factors, which although not transcriptionally deregulated per se, organise aberrant gene regulatory networks that help identify myeloma cell dependencies with prognostic impact. Finally, we identify and validate the critical super-enhancer that regulates ectopic expression of CCND2 in a subset of patients with MM and in chronic lymphocytic leukemia. |
| first_indexed | 2024-03-07T06:23:33Z |
| format | Journal article |
| id | oxford-uuid:f37cb0a2-b39d-4fac-8e1c-4c876fdaedbb |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:23:33Z |
| publishDate | 2021 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:f37cb0a2-b39d-4fac-8e1c-4c876fdaedbb2022-03-27T12:12:33ZChromatin-based, in cis and in trans regulatory rewiring underpins distinct oncogenic transcriptomes in multiple myelomaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f37cb0a2-b39d-4fac-8e1c-4c876fdaedbbEnglishSymplectic ElementsSpringer Nature2021Alvarez-Benayas, JTrasanidis, NKatsarou, APonnusamy, KChaidos, AMay, PCXiao, XBua, MAtta, MRoberts, IAGAuner, HWHatjiharissi, EPapaioannou, MCaputo, VSSudbery, IMKaradimitris, AMultiple myeloma is a genetically heterogeneous cancer of the bone marrow plasma cells (PC). Distinct myeloma transcriptome profiles are primarily driven by myeloma initiating events (MIE) and converge into a mutually exclusive overexpression of the CCND1 and CCND2 oncogenes. Here, with reference to their normal counterparts, we find that myeloma PC enhanced chromatin accessibility combined with paired transcriptome profiling can classify MIE-defined genetic subgroups. Across and within different MM genetic subgroups, we ascribe regulation of genes and pathways critical for myeloma biology to unique or shared, developmentally activated or de novo formed candidate enhancers. Such enhancers co-opt recruitment of existing transcription factors, which although not transcriptionally deregulated per se, organise aberrant gene regulatory networks that help identify myeloma cell dependencies with prognostic impact. Finally, we identify and validate the critical super-enhancer that regulates ectopic expression of CCND2 in a subset of patients with MM and in chronic lymphocytic leukemia. |
| spellingShingle | Alvarez-Benayas, J Trasanidis, N Katsarou, A Ponnusamy, K Chaidos, A May, PC Xiao, X Bua, M Atta, M Roberts, IAG Auner, HW Hatjiharissi, E Papaioannou, M Caputo, VS Sudbery, IM Karadimitris, A Chromatin-based, in cis and in trans regulatory rewiring underpins distinct oncogenic transcriptomes in multiple myeloma |
| title | Chromatin-based, in cis and in trans regulatory rewiring underpins distinct oncogenic transcriptomes in multiple myeloma |
| title_full | Chromatin-based, in cis and in trans regulatory rewiring underpins distinct oncogenic transcriptomes in multiple myeloma |
| title_fullStr | Chromatin-based, in cis and in trans regulatory rewiring underpins distinct oncogenic transcriptomes in multiple myeloma |
| title_full_unstemmed | Chromatin-based, in cis and in trans regulatory rewiring underpins distinct oncogenic transcriptomes in multiple myeloma |
| title_short | Chromatin-based, in cis and in trans regulatory rewiring underpins distinct oncogenic transcriptomes in multiple myeloma |
| title_sort | chromatin based in cis and in trans regulatory rewiring underpins distinct oncogenic transcriptomes in multiple myeloma |
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