Logo: to the web site of Uppsala University

uu.sePublications from Uppsala University
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Linked-read whole-genome sequencing resolves common and private structural variants in multiple myeloma
Karolinska Inst, Dept Lab Med, Stockholm, Sweden.;Karolinska Inst, Ctr Hematol & Regenerat Med, Stockholm, Sweden..ORCID iD: 0000-0002-5044-7754
Karolinska Inst, Dept Lab Med, Stockholm, Sweden.;Karolinska Inst, Ctr Hematol & Regenerat Med, Stockholm, Sweden..ORCID iD: 0000-0003-1834-7638
Karolinska Inst, Dept Lab Med, Stockholm, Sweden.;Karolinska Inst, Ctr Hematol & Regenerat Med, Stockholm, Sweden..ORCID iD: 0000-0001-6674-4297
Karolinska Inst, Ctr Hematol & Regenerat Med, Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden..
Show others and affiliations
2022 (English)In: Blood Advances, ISSN 2473-9529 , E-ISSN 2473-9537, Vol. 6, no 17, p. 5009-5023Article in journal (Refereed) Published
Abstract [en]

Multiple myeloma (MM) is an incurable and aggressive plasma cell malignancy characterized by a complex karyotype with multiple structural variants (SVs) and copy-number variations (CNVs). Linked-read whole-genome sequencing (lrWGS) allows for refined detection and reconstruction of SVs by providing long-range genetic information from standard short-read sequencing. This makes lrWGS an attractive solution for capturing the full genomic complexity of MM. Here we show that high-quality lrWGS data can be generated from low numbers of cells subjected to fluorescence-activated cell sorting (FACS) without DNA purification. Using this protocol, we analyzed MM cells after FACS from 37 patients with MM using lrWGS. We found high concordance between lrWGS and fluorescence in situ hybridization (FISH) for the detection of recurrent translocations and CNVs. Outside of the regions investigated by FISH, we identified > 150 additional SVs and CNVs across the cohort. Analysis of the lrWGS data allowed for resolution of the structure of diverse SVs affecting the MYC and t(11;14) loci, causing the duplication of genes and gene regulatory elements. In addition, we identified private SVs causing the dysregulation of genes recurrently involved in translocations with the IGH locus and show that these can alter the molecular classification of MM. Overall, we conclude that lrWGS allows for the detection of aberrations critical for MM prognostics and provides a feasible route for providing comprehensive genetics. Implementing lrWGS could provide more accurate clinical prognostics, facilitate genomic medicine initiatives, and greatly improve the stratification of patients included in clinical trials.

Place, publisher, year, edition, pages
American Society of Hematology, 2022. Vol. 6, no 17, p. 5009-5023
National Category
Hematology Genetics and Genomics
Identifiers
URN: urn:nbn:se:uu:diva-495792DOI: 10.17044/scilifelab.17049059.v1ISI: 000877428400002PubMedID: 35675515OAI: oai:DiVA.org:uu-495792DiVA, id: diva2:1733638
Funder
Swedish Cancer SocietySwedish Research CouncilSwedish Foundation for Strategic ResearchKnut and Alice Wallenberg FoundationAvailable from: 2023-02-02 Created: 2023-02-02 Last updated: 2025-02-01Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Authority records

Kierczak, Marcin

Search in DiVA

By author/editor
Pena-Perez, LuciaFrengen, NicolaiHauenstein, JuliaKierczak, MarcinTaborsak-Lines, Fanny
By organisation
Science for Life Laboratory, SciLifeLabDepartment of Medical Biochemistry and Microbiology
In the same journal
Blood Advances
HematologyGenetics and Genomics

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 48 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf