Whole-genome optical mapping of bone-marrow myeloma cells reveals association of extramedullary multiple myeloma with chromosome 1 abnormalities

Abstract 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 G...

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Autores principales:	Eva Kriegova, Regina Fillerova, Jiri Minarik, Jakub Savara, Jirina Manakova, Anna Petrackova, Martin Dihel, Jana Balcarkova, Petra Krhovska, Tomas Pika, Petr Gajdos, Marek Behalek, Michal Vasinek, Tomas Papajik
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/37daeaba58954dc38da078cfcf51a94f
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spelling	oai:doaj.org-article:37daeaba58954dc38da078cfcf51a94f2021-12-02T16:17:33ZWhole-genome optical mapping of bone-marrow myeloma cells reveals association of extramedullary multiple myeloma with chromosome 1 abnormalities10.1038/s41598-021-93835-z2045-2322https://doaj.org/article/37daeaba58954dc38da078cfcf51a94f2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93835-zhttps://doaj.org/toc/2045-2322Abstract 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.Eva KriegovaRegina FillerovaJiri MinarikJakub SavaraJirina ManakovaAnna PetrackovaMartin DihelJana BalcarkovaPetra KrhovskaTomas PikaPetr GajdosMarek BehalekMichal VasinekTomas PapajikNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Eva Kriegova Regina Fillerova Jiri Minarik Jakub Savara Jirina Manakova Anna Petrackova Martin Dihel Jana Balcarkova Petra Krhovska Tomas Pika Petr Gajdos Marek Behalek Michal Vasinek Tomas Papajik Whole-genome optical mapping of bone-marrow myeloma cells reveals association of extramedullary multiple myeloma with chromosome 1 abnormalities
description	Abstract 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.
format	article
author	Eva Kriegova Regina Fillerova Jiri Minarik Jakub Savara Jirina Manakova Anna Petrackova Martin Dihel Jana Balcarkova Petra Krhovska Tomas Pika Petr Gajdos Marek Behalek Michal Vasinek Tomas Papajik
author_facet	Eva Kriegova Regina Fillerova Jiri Minarik Jakub Savara Jirina Manakova Anna Petrackova Martin Dihel Jana Balcarkova Petra Krhovska Tomas Pika Petr Gajdos Marek Behalek Michal Vasinek Tomas Papajik
author_sort	Eva Kriegova
title	Whole-genome optical mapping of bone-marrow myeloma cells reveals association of extramedullary multiple myeloma with chromosome 1 abnormalities
title_short	Whole-genome optical mapping of bone-marrow myeloma cells reveals association of extramedullary multiple myeloma with chromosome 1 abnormalities
title_full	Whole-genome optical mapping of bone-marrow myeloma cells reveals association of extramedullary multiple myeloma with chromosome 1 abnormalities
title_fullStr	Whole-genome optical mapping of bone-marrow myeloma cells reveals association of extramedullary multiple myeloma with chromosome 1 abnormalities
title_full_unstemmed	Whole-genome optical mapping of bone-marrow myeloma cells reveals association of extramedullary multiple myeloma with chromosome 1 abnormalities
title_sort	whole-genome optical mapping of bone-marrow myeloma cells reveals association of extramedullary multiple myeloma with chromosome 1 abnormalities
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/37daeaba58954dc38da078cfcf51a94f
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Whole-genome optical mapping of bone-marrow myeloma cells reveals association of extramedullary multiple myeloma with chromosome 1 abnormalities

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