Whole-genome optical mapping of bone-marrow myeloma cells reveals association of extramedullary multiple myeloma with chromosome 1 abnormalities.
Aged
Aged, 80 and over
Bone Marrow
/ diagnostic imaging
Bone Marrow Cells
/ pathology
Chromosome Aberrations
Chromosomes, Human, Pair 1
/ genetics
Cohort Studies
Cytogenetic Analysis
/ methods
Czech Republic
Female
Genome-Wide Association Study
/ methods
Humans
Male
Middle Aged
Multiple Myeloma
/ genetics
Pilot Projects
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
19 07 2021
19 07 2021
Historique:
received:
01
02
2021
accepted:
24
06
2021
entrez:
20
7
2021
pubmed:
21
7
2021
medline:
30
11
2021
Statut:
epublish
Résumé
Extramedullary disease (EMM) represents a rare, aggressive and mostly resistant phenotype of multiple myeloma (MM). EMM is frequently associated with high-risk cytogenetics, but their complex genomic architecture is largely unexplored. We used whole-genome optical mapping (Saphyr, Bionano Genomics) to analyse the genomic architecture of CD138+ cells isolated from bone-marrow aspirates from an unselected cohort of newly diagnosed patients with EMM (n = 4) and intramedullary MM (n = 7). Large intrachromosomal rearrangements (> 5 Mbp) within chromosome 1 were detected in all EMM samples. These rearrangements, predominantly deletions with/without inversions, encompassed hundreds of genes and led to changes in the gene copy number on large regions of chromosome 1. Compared with intramedullary MM, EMM was characterised by more deletions (size range of 500 bp-50 kbp) and fewer interchromosomal translocations, and two EMM samples had copy number loss in the 17p13 region. Widespread genomic heterogeneity and novel aberrations in the high-risk IGH/IGK/IGL, 8q24 and 13q14 regions were detected in individual patients but were not specific to EMM/MM. Our pilot study revealed an association of chromosome 1 abnormalities in bone marrow myeloma cells with extramedullary progression. Optical mapping showed the potential for refining the complex genomic architecture in MM and its phenotypes.
Identifiants
pubmed: 34282158
doi: 10.1038/s41598-021-93835-z
pii: 10.1038/s41598-021-93835-z
pmc: PMC8289962
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
14671Informations de copyright
© 2021. The Author(s).
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