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  • Ali, MinaLund University,Lunds universitet,Hematogenomics,Forskargrupper vid Lunds universitet,Lund University Research Groups (author)

The multiple myeloma risk allele at 5q15 lowers ELL2 expression and increases ribosomal gene expression

  • Article/chapterEnglish2018

Publisher, publication year, extent ...

  • 2018-04-25
  • Springer Science and Business Media LLC,2018

Numbers

  • LIBRIS-ID:oai:prod.swepub.kib.ki.se:138118668
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:138118668URI
  • https://doi.org/10.1038/s41467-018-04082-2DOI
  • https://lup.lub.lu.se/record/60969839-f43a-4be0-aaa1-c1b4599e1ba7URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Recently, we identified ELL2 as a susceptibility gene for multiple myeloma (MM). To understand its mechanism of action, we performed expression quantitative trait locus analysis in CD138+ plasma cells from 1630 MM patients from four populations. We show that the MM risk allele lowers ELL2 expression in these cells (Pcombined = 2.5 × 10−27; βcombined = −0.24 SD), but not in peripheral blood or other tissues. Consistent with this, several variants representing the MM risk allele map to regulatory genomic regions, and three yield reduced transcriptional activity in plasmocytoma cell lines. One of these (rs3777189-C) co-locates with the best-supported lead variants for ELL2 expression and MM risk, and reduces binding of MAFF/G/K family transcription factors. Moreover, further analysis reveals that the MM risk allele associates with upregulation of gene sets related to ribosome biogenesis, and knockout/knockdown and rescue experiments in plasmocytoma cell lines support a cause–effect relationship. Our results provide mechanistic insight into MM predisposition.

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  • Ajore, RamLund University,Lunds universitet,Hematogenomics,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)med-rao (author)
  • Wihlborg, Anna KarinLund University,Lunds universitet,Hematogenomics,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)kard-awi (author)
  • Niroula, AbhishekLund University,Lunds universitet,Hematogenomics,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)med-anu (author)
  • Swaminathan, BhairaviLund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)med-bvs (author)
  • Johnsson, EllinorLund University,Lunds universitet,Hematogenomics,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)efor-ejo (author)
  • Stephens, OWUniversity of Arkansas for Medical Sciences (author)
  • Morgan, GUniversity of Arkansas for Medical Sciences (author)
  • Meissner, TAvera Cancer Institute (author)
  • Turesson, IngemarLund University,Lunds universitet,Myelomgruppen,Forskargrupper vid Lunds universitet,Myeloma research group,Lund University Research Groups(Swepub:lu)medf-itu (author)
  • Goldschmidt, HGerman Cancer Research Centre,Heidelberg University (author)
  • Mellqvist, UH (author)
  • Gullberg, UrbanLund University,Lunds universitet,Undersökning av molekylära sjukdomsmekanismer vid blodcancer,Forskargrupper vid Lunds universitet,Transcriptional mechanisms for the Wilms’ tumor gene 1 (WT1) oncoprotein,Lund University Research Groups(Swepub:lu)efor-ugu (author)
  • Hansson, MarkusLund University,Lunds universitet,Myelomgruppen,Forskargrupper vid Lunds universitet,Myeloma research group,Lund University Research Groups,Skåne University Hospital(Swepub:lu)hema-mha (author)
  • Hemminki, KariLund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups,German Cancer Research Centre(Swepub:lu)med-khk (author)
  • Nahi, HKarolinska Institutet (author)
  • Waage, ANorwegian University of Science and Technology (author)
  • Weinhold, NUniversity of Arkansas for Medical Sciences (author)
  • Nilsson, BjörnLund University,Lunds universitet,Hematogenomics,Forskargrupper vid Lunds universitet,Lund University Research Groups,Broad Institute(Swepub:lu)klin-bni (author)
  • HematogenomicsForskargrupper vid Lunds universitet (creator_code:org_t)

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  • In:Nature communications: Springer Science and Business Media LLC9:1, s. 1649-2041-1723

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