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Linked-read whole-g...
Linked-read whole-genome sequencing resolves common and private structural variants in multiple myeloma
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- Peña-Pérez, L. (författare)
- Karolinska Institutet
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- Frengen, N. (författare)
- Karolinska Institutet
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- Hauenstein, J. (författare)
- Karolinska Institutet
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- Gran, C. (författare)
- Karolinska Institutet
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- Gustafsson, C. (författare)
- Karolinska Institutet
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- Eisfeldt, J. (författare)
- Karolinska Institutet
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- Kierczak, M. (författare)
- Uppsala Univ, Dept Cell & Mol Biol, Sci Life Lab, Natl Bioinformat Infrastruct Sweden, Uppsala, Sweden.
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- Taborsak-Lines, Fanny (författare)
- KTH,Genteknologi
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- Olsen, Remi-André (författare)
- Stockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab),Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, Stockholm, Sweden.
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- Wallblom, A. (författare)
- Karolinska Inst, Ctr Hematol & Regenerat Med, Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden.
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- Krstic, A. (författare)
- Karolinska Institutet
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- Ewels, Philip (författare)
- Stockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab),Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, Stockholm, Sweden.
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- Lindstrand, A. (författare)
- Karolinska Institutet
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- Månsson, R. (författare)
- Karolinska Institutet
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Karolinska Institutet Uppsala Univ, Dept Cell & Mol Biol, Sci Life Lab, Natl Bioinformat Infrastruct Sweden, Uppsala, Sweden (creator_code:org_t)
- 2022-08-30
- 2022
- Engelska.
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 6:17, s. 5009-5023
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Nyckelord
- immunoglobulin heavy chain
- Article
- cancer classification
- cancer genetics
- cancer prognosis
- cell count
- clinical article
- cohort analysis
- controlled study
- DNA purification
- feasibility study
- fluorescence activated cell sorting
- fluorescence in situ hybridization
- gene control
- gene duplication
- gene locus
- gene structure
- gene translocation
- genetic variability
- human
- human cell
- human genome
- human tissue
- linked read whole genome sequencing
- molecular genetics
- multiple myeloma
- myeloma cell
- oncogene myc
- quality control
- whole genome sequencing
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Peña-Pérez, L.
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Frengen, N.
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Hauenstein, J.
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Gran, C.
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Gustafsson, C.
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Eisfeldt, J.
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visa fler...
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Kierczak, M.
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Taborsak-Lines, ...
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Olsen, Remi-Andr ...
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Wallblom, A.
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Krstic, A.
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Ewels, Philip
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Lindstrand, A.
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Månsson, R.
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visa färre...
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Blood Advances
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Stockholms universitet
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Kungliga Tekniska Högskolan
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Karolinska Institutet