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Myeloma immunoglobulin rearrangement and translocation detection through targeted capture sequencing

Multiple myeloma is a plasma cell neoplasm characterized by clonal immunoglobulin V(D)J signatures and oncogenic immunoglobulin gene translocations. Additional subclonal genomic changes are acquired with myeloma progression and therapeutic selection. PCR-based methods to detect V(D)J rearrangements...

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Autores principales: Chow, Signy, Kis, Olena, Mulder, David T, Danesh, Arnavaz, Bruce, Jeff, Wang, Ting Ting, Reece, Donna, Bhalis, Nizar, Neri, Paola, Sabatini, Peter JB, Keats, Jonathan, Trudel, Suzanne, Pugh, Trevor J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Life Science Alliance LLC 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9644417/
https://www.ncbi.nlm.nih.gov/pubmed/36328595
http://dx.doi.org/10.26508/lsa.202201543
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author Chow, Signy
Kis, Olena
Mulder, David T
Danesh, Arnavaz
Bruce, Jeff
Wang, Ting Ting
Reece, Donna
Bhalis, Nizar
Neri, Paola
Sabatini, Peter JB
Keats, Jonathan
Trudel, Suzanne
Pugh, Trevor J
author_facet Chow, Signy
Kis, Olena
Mulder, David T
Danesh, Arnavaz
Bruce, Jeff
Wang, Ting Ting
Reece, Donna
Bhalis, Nizar
Neri, Paola
Sabatini, Peter JB
Keats, Jonathan
Trudel, Suzanne
Pugh, Trevor J
author_sort Chow, Signy
collection PubMed
description Multiple myeloma is a plasma cell neoplasm characterized by clonal immunoglobulin V(D)J signatures and oncogenic immunoglobulin gene translocations. Additional subclonal genomic changes are acquired with myeloma progression and therapeutic selection. PCR-based methods to detect V(D)J rearrangements can have biases introduced by highly multiplexed reactions and primers undermined by somatic hypermutation, and are not readily extended to include mutation detection. Here, we report a hybrid-capture approach (CapIG-seq) targeting the 3′ and 5′ ends of the V and J segments of all immunoglobulin loci that enable the efficient detection of V(D)J rearrangements. We also included baits for oncogenic translocations and mutation detection. We demonstrate complete concordance with matched whole-genome sequencing and/or PCR clonotyping of 24 cell lines and report the clonal sequences for 41 uncharacterized cell lines. We also demonstrate the application to patient specimens, including 29 bone marrow and 39 cell-free DNA samples. CapIG-seq shows concordance between bone marrow and cfDNA blood samples (both contemporaneous and follow-up) with regard to the somatic variant, V(D)J, and translocation detection. CapIG-seq is a novel, efficient approach to examining genomic alterations in myeloma.
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spelling pubmed-96444172022-11-15 Myeloma immunoglobulin rearrangement and translocation detection through targeted capture sequencing Chow, Signy Kis, Olena Mulder, David T Danesh, Arnavaz Bruce, Jeff Wang, Ting Ting Reece, Donna Bhalis, Nizar Neri, Paola Sabatini, Peter JB Keats, Jonathan Trudel, Suzanne Pugh, Trevor J Life Sci Alliance Resources Multiple myeloma is a plasma cell neoplasm characterized by clonal immunoglobulin V(D)J signatures and oncogenic immunoglobulin gene translocations. Additional subclonal genomic changes are acquired with myeloma progression and therapeutic selection. PCR-based methods to detect V(D)J rearrangements can have biases introduced by highly multiplexed reactions and primers undermined by somatic hypermutation, and are not readily extended to include mutation detection. Here, we report a hybrid-capture approach (CapIG-seq) targeting the 3′ and 5′ ends of the V and J segments of all immunoglobulin loci that enable the efficient detection of V(D)J rearrangements. We also included baits for oncogenic translocations and mutation detection. We demonstrate complete concordance with matched whole-genome sequencing and/or PCR clonotyping of 24 cell lines and report the clonal sequences for 41 uncharacterized cell lines. We also demonstrate the application to patient specimens, including 29 bone marrow and 39 cell-free DNA samples. CapIG-seq shows concordance between bone marrow and cfDNA blood samples (both contemporaneous and follow-up) with regard to the somatic variant, V(D)J, and translocation detection. CapIG-seq is a novel, efficient approach to examining genomic alterations in myeloma. Life Science Alliance LLC 2022-11-03 /pmc/articles/PMC9644417/ /pubmed/36328595 http://dx.doi.org/10.26508/lsa.202201543 Text en © 2022 Chow et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Resources
Chow, Signy
Kis, Olena
Mulder, David T
Danesh, Arnavaz
Bruce, Jeff
Wang, Ting Ting
Reece, Donna
Bhalis, Nizar
Neri, Paola
Sabatini, Peter JB
Keats, Jonathan
Trudel, Suzanne
Pugh, Trevor J
Myeloma immunoglobulin rearrangement and translocation detection through targeted capture sequencing
title Myeloma immunoglobulin rearrangement and translocation detection through targeted capture sequencing
title_full Myeloma immunoglobulin rearrangement and translocation detection through targeted capture sequencing
title_fullStr Myeloma immunoglobulin rearrangement and translocation detection through targeted capture sequencing
title_full_unstemmed Myeloma immunoglobulin rearrangement and translocation detection through targeted capture sequencing
title_short Myeloma immunoglobulin rearrangement and translocation detection through targeted capture sequencing
title_sort myeloma immunoglobulin rearrangement and translocation detection through targeted capture sequencing
topic Resources
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9644417/
https://www.ncbi.nlm.nih.gov/pubmed/36328595
http://dx.doi.org/10.26508/lsa.202201543
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