RT Journal Article
SR Electronic
T1 Myeloma immunoglobulin rearrangement and translocation detection through targeted capture sequencing
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202201543
DO 10.26508/lsa.202201543
VO 6
IS 1
A1 Chow, Signy
A1 Kis, Olena
A1 Mulder, David T
A1 Danesh, Arnavaz
A1 Bruce, Jeff
A1 Wang, Ting Ting
A1 Reece, Donna
A1 Bhalis, Nizar
A1 Neri, Paola
A1 Sabatini, Peter JB
A1 Keats, Jonathan
A1 Trudel, Suzanne
A1 Pugh, Trevor J
YR 2023
UL http://www.life-science-alliance.org/content/6/1/e202201543.abstract
AB 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.