PMID- 35675515
OWN - NLM
STAT- MEDLINE
DCOM- 20220902
LR  - 20221105
IS  - 2473-9537 (Electronic)
IS  - 2473-9529 (Print)
IS  - 2473-9529 (Linking)
VI  - 6
IP  - 17
DP  - 2022 Sep 13
TI  - Linked-read whole-genome sequencing resolves common and private structural 
      variants in multiple myeloma.
PG  - 5009-5023
LID - 10.1182/bloodadvances.2021006720 [doi]
AB  - 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.
CI  - (c) 2022 by The American Society of Hematology. Licensed under Creative Commons 
      Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), 
      permitting only noncommercial, nonderivative use with attribution. All other 
      rights reserved.
FAU - Pena-Perez, Lucia
AU  - Pena-Perez L
AUID- ORCID: 0000-0002-5044-7754
AD  - Department of Laboratory Medicine.
AD  - Center for Hematology and Regenerative Medicine.
FAU - Frengen, Nicolai
AU  - Frengen N
AUID- ORCID: 0000-0003-1834-7638
AD  - Department of Laboratory Medicine.
AD  - Center for Hematology and Regenerative Medicine.
FAU - Hauenstein, Julia
AU  - Hauenstein J
AUID- ORCID: 0000-0001-6674-4297
AD  - Department of Laboratory Medicine.
AD  - Center for Hematology and Regenerative Medicine.
FAU - Gran, Charlotte
AU  - Gran C
AD  - Center for Hematology and Regenerative Medicine.
AD  - Department of Medicine, and.
FAU - Gustafsson, Charlotte
AU  - Gustafsson C
AD  - Department of Laboratory Medicine.
AD  - Center for Hematology and Regenerative Medicine.
FAU - Eisfeldt, Jesper
AU  - Eisfeldt J
AD  - Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, 
      Sweden.
AD  - Science for Life Laboratory, Karolinska Institutet Science Park, Stockholm, 
      Sweden.
FAU - Kierczak, Marcin
AU  - Kierczak M
AD  - Department of Cell and Molecular Biology, National Bioinformatics Infrastructure 
      Sweden, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
FAU - Taborsak-Lines, Fanny
AU  - Taborsak-Lines F
AUID- ORCID: 0000-0001-7198-5116
AD  - Division of Gene Technology, Royal Institute of Technology, Stockholm, Sweden.
FAU - Olsen, Remi-Andre
AU  - Olsen RA
AD  - Department of Biochemistry and Biophysics, Science for Life Laboratory, Stockholm 
      University, Stockholm, Sweden; and.
FAU - Wallblom, Ann
AU  - Wallblom A
AD  - Center for Hematology and Regenerative Medicine.
AD  - Department of Medicine, and.
FAU - Krstic, Aleksandra
AU  - Krstic A
AD  - Department of Clinical Pathology and Cytology.
FAU - Ewels, Philip
AU  - Ewels P
AD  - Department of Biochemistry and Biophysics, Science for Life Laboratory, Stockholm 
      University, Stockholm, Sweden; and.
FAU - Lindstrand, Anna
AU  - Lindstrand A
AD  - Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, 
      Sweden.
AD  - Department of Clinical Genetics, and.
FAU - Mansson, Robert
AU  - Mansson R
AUID- ORCID: 0000-0003-0738-0328
AD  - Department of Laboratory Medicine.
AD  - Center for Hematology and Regenerative Medicine.
AD  - Department of Hematology, Karolinska University Hospital, Stockholm, Sweden.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood Adv
JT  - Blood advances
JID - 101698425
SB  - IM
MH  - DNA Copy Number Variations
MH  - Genomics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - *Multiple Myeloma/diagnosis/genetics
MH  - Translocation, Genetic
MH  - Whole Genome Sequencing
PMC - PMC9631623
EDAT- 2022/06/09 06:00
MHDA- 2022/09/03 06:00
PMCR- 2022/08/30
CRDT- 2022/06/08 15:02
PHST- 2021/11/29 00:00 [received]
PHST- 2022/05/31 00:00 [accepted]
PHST- 2022/06/09 06:00 [pubmed]
PHST- 2022/09/03 06:00 [medline]
PHST- 2022/06/08 15:02 [entrez]
PHST- 2022/08/30 00:00 [pmc-release]
AID - 485485 [pii]
AID - 2022/ADV2021006720 [pii]
AID - 10.1182/bloodadvances.2021006720 [doi]
PST - ppublish
SO  - Blood Adv. 2022 Sep 13;6(17):5009-5023. doi: 10.1182/bloodadvances.2021006720.