TY - JOUR
T1 - Comprehensive detection of recurring genomic abnormalities
T2 - a targeted sequencing approach for multiple myeloma
AU - Yellapantula, Venkata
AU - Hultcrantz, Malin
AU - Rustad, Even H.
AU - Wasserman, Ester
AU - Londono, Dory
AU - Cimera, Robert
AU - Ciardiello, Amanda
AU - Landau, Heather
AU - Akhlaghi, Theresia
AU - Mailankody, Sham
AU - Patel, Minal
AU - Medina-Martinez, Juan Santiago
AU - Arango Ossa, Juan Esteban
AU - Levine, Max Fine
AU - Bolli, Niccolo
AU - Maura, Francesco
AU - Dogan, Ahmed
AU - Papaemmanuil, Elli
AU - Zhang, Yanming
AU - Landgren, Ola
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Recent genomic research efforts in multiple myeloma have revealed clinically relevant molecular subgroups beyond conventional cytogenetic classifications. Implementing these advances in clinical trial design and in routine patient care requires a new generation of molecular diagnostic tools. Here, we present a custom capture next-generation sequencing (NGS) panel designed to identify rearrangements involving the IGH locus, arm level, and focal copy number aberrations, as well as frequently mutated genes in multiple myeloma in a single assay. We sequenced 154 patients with plasma cell disorders and performed a head-to-head comparison with the results from conventional clinical assays, i.e., fluorescent in situ hybridization (FISH) and single-nucleotide polymorphism (SNP) microarray. Our custom capture NGS panel had high sensitivity (>99%) and specificity (>99%) for detection of IGH translocations and relevant chromosomal gains and losses in multiple myeloma. In addition, the assay was able to capture novel genomic markers associated with poor outcome such as bi-allelic events involving TP53. In summary, we show that a multiple myeloma designed custom capture NGS panel can detect IGH translocations and CNAs with very high concordance in relation to FISH and SNP microarrays and importantly captures the most relevant and recurrent somatic mutations in multiple myeloma rendering this approach highly suitable for clinical application in the modern era.
AB - Recent genomic research efforts in multiple myeloma have revealed clinically relevant molecular subgroups beyond conventional cytogenetic classifications. Implementing these advances in clinical trial design and in routine patient care requires a new generation of molecular diagnostic tools. Here, we present a custom capture next-generation sequencing (NGS) panel designed to identify rearrangements involving the IGH locus, arm level, and focal copy number aberrations, as well as frequently mutated genes in multiple myeloma in a single assay. We sequenced 154 patients with plasma cell disorders and performed a head-to-head comparison with the results from conventional clinical assays, i.e., fluorescent in situ hybridization (FISH) and single-nucleotide polymorphism (SNP) microarray. Our custom capture NGS panel had high sensitivity (>99%) and specificity (>99%) for detection of IGH translocations and relevant chromosomal gains and losses in multiple myeloma. In addition, the assay was able to capture novel genomic markers associated with poor outcome such as bi-allelic events involving TP53. In summary, we show that a multiple myeloma designed custom capture NGS panel can detect IGH translocations and CNAs with very high concordance in relation to FISH and SNP microarrays and importantly captures the most relevant and recurrent somatic mutations in multiple myeloma rendering this approach highly suitable for clinical application in the modern era.
UR - http://www.scopus.com/inward/record.url?scp=85076470042&partnerID=8YFLogxK
U2 - 10.1038/s41408-019-0264-y
DO - 10.1038/s41408-019-0264-y
M3 - Article
C2 - 31827071
AN - SCOPUS:85076470042
SN - 2044-5385
VL - 9
JO - Blood Cancer Journal
JF - Blood Cancer Journal
IS - 12
M1 - 101
ER -