dc.date.accessioned | 2022-11-22T17:33:48Z | |
dc.date.available | 2022-11-22T17:33:48Z | |
dc.date.created | 2022-09-05T12:56:57Z | |
dc.date.issued | 2022 | |
dc.identifier.citation | Misund, Kristine Hofste op Bruinink, Davine Coward, Eivind Hoogenboezem, Remco M. Rustad, Even Holth Sanders, Mathijs A. Rye, Morten Beck Sponaas, Anne-Marit van der Holt, Bronno Zweegman, Sonja Hovig, Eivind Meza, Leonardo Zepeda Sundan, Anders Myklebost, Ola Sonneveld, Pieter Waage, Anders . Clonal evolution after treatment pressure in multiple myeloma: heterogenous genomic aberrations and transcriptomic convergence. Leukemia. 2022, 36(7), 1887-1897 | |
dc.identifier.uri | http://hdl.handle.net/10852/97713 | |
dc.description.abstract | Abstract We investigated genomic and transcriptomic changes in paired tumor samples of 29 in-house multiple myeloma (MM) patients and 28 patients from the MMRF CoMMpass study before and after treatment. A change in clonal composition was found in 46/57 (82%) of patients, and single-nucleotide variants (SNVs) increased from median 67 to 86. The highest increase in prevalence of genetic aberrations was found in RAS genes (60% to 72%), amp1q21 (18% to 35%), and TP53 (9% to 18%). The SBS-MM1 mutation signature was detected both in patients receiving high and low dose melphalan. A total of 2589 genes were differentially expressed between early and late samples (FDR < 0.05). Gene set enrichment analysis (GSEA) showed increased expression of E2F, MYC, and glycolysis pathways and a decreased expression in TNF-NFkB and TGFbeta pathways in late compared to early stage. Single sample GSEA (ssGSEA) scores of differentially expressed pathways revealed that these changes were most evident in end-stage disease. Increased expression of several potentially targetable genes was found at late disease stages, including cancer-testis antigens, XPO1 and ABC transporters. Our study demonstrates a transcriptomic convergence of pathways supporting increased proliferation and metabolism during disease progression in MM. | |
dc.language | EN | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.title | Clonal evolution after treatment pressure in multiple myeloma: heterogenous genomic aberrations and transcriptomic convergence | |
dc.title.alternative | ENEngelskEnglishClonal evolution after treatment pressure in multiple myeloma: heterogenous genomic aberrations and transcriptomic convergence | |
dc.type | Journal article | |
dc.creator.author | Misund, Kristine | |
dc.creator.author | Hofste op Bruinink, Davine | |
dc.creator.author | Coward, Eivind | |
dc.creator.author | Hoogenboezem, Remco M. | |
dc.creator.author | Rustad, Even Holth | |
dc.creator.author | Sanders, Mathijs A. | |
dc.creator.author | Rye, Morten Beck | |
dc.creator.author | Sponaas, Anne-Marit | |
dc.creator.author | van der Holt, Bronno | |
dc.creator.author | Zweegman, Sonja | |
dc.creator.author | Hovig, Eivind | |
dc.creator.author | Meza, Leonardo Zepeda | |
dc.creator.author | Sundan, Anders | |
dc.creator.author | Myklebost, Ola | |
dc.creator.author | Sonneveld, Pieter | |
dc.creator.author | Waage, Anders | |
cristin.unitcode | 185,15,31,0 | |
cristin.unitname | Senter for bioinformatikk | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 2 | |
dc.identifier.cristin | 2048872 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Leukemia&rft.volume=36&rft.spage=1887&rft.date=2022 | |
dc.identifier.jtitle | Leukemia | |
dc.identifier.volume | 36 | |
dc.identifier.issue | 7 | |
dc.identifier.startpage | 1887 | |
dc.identifier.endpage | 1897 | |
dc.identifier.doi | https://doi.org/10.1038/s41375-022-01597-y | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 0887-6924 | |
dc.type.version | PublishedVersion | |