Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Dec 11;9(12):101.
doi: 10.1038/s41408-019-0264-y.

Comprehensive detection of recurring genomic abnormalities: a targeted sequencing approach for multiple myeloma

Venkata Yellapantula  1 , Malin Hultcrantz  2   3 , Even H Rustad  1 , Ester Wasserman  4 , Dory Londono  4 , Robert Cimera  4 , Amanda Ciardiello  1 , Heather Landau  5 , Theresia Akhlaghi  1 , Sham Mailankody  1 , Minal Patel  6 , Juan Santiago Medina-Martinez  6 , Juan Esteban Arango Ossa  6 , Max Fine Levine  6 , Niccolo Bolli  7   8 , Francesco Maura  1 , Ahmet Dogan  9 , Elli Papaemmanuil  6   10 , Yanming Zhang  11 , Ola Landgren  12
Affiliations

Comprehensive detection of recurring genomic abnormalities: a targeted sequencing approach for multiple myeloma

Venkata Yellapantula et al. Blood Cancer J. .

Erratum in

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

M.H. has received funding from the Multiple Myeloma Research Foundation, the Swedish Research Council, the Swedish Cancer Society, Karolinska Institute Foundations, and the Swedish Blood Cancer Foundation. N.B. has received Honoraria/ad boards from: Celgene, Janssen, Novartis. E.H. is a Josie Robertson Investigator, an EHA Fellow, and an ASH Scholar. O.L. has received research funding from: National Institutes of Health (NIH), U.S. Food and Drug Administration (FDA), Multiple Myeloma Research Foundation (MMRF), International Myeloma Foundation (IMF), Leukemia and Lymphoma Society (LLS), Perelman Family Foundation, Rising Tides Foundation, Amgen, Celgene, Janssen, Takeda, Glenmark, Seattle Genetics, Karyopharm; Honoraria/ad boards: Adaptive, Amgen, Binding Site, BMS, Celgene, Cellectis, Glenmark, Janssen, Juno, Pfizer; and serves on Independent Data Monitoring Committees (IDMCs) for clinical trials lead by Takeda, Merck, Janssen, and Theradex. There is a pending patent application regarding the myTYPE assay (M.H., E.P., and O.L.). The remaining authors declare no relevant conflicts of interest.

Figures

Fig. 1
Fig. 1
a IGH translocations, copy number alterations, and somatic mutations captured with myTYPE targeted sequencing. b Number of events in relation to disease status.
Fig. 2
Fig. 2
a Sample purity estimates SNP microarray and b correlation between sample purity estimated by SNP microarray and myTYPE sequencing.
Fig. 3
Fig. 3
Concordance and discordance for the detection of genomic aberrations: multiple myeloma targeted FISH and SNP microarray versus myTYPE.
Fig. 4
Fig. 4
Comparison of multiple myeloma targeted FISH and SNP microarray versus myTYPE.
Fig. 5
Fig. 5
a Distribution of somatic mutations in selected tumor suppressor genes. b Bi-allelic events detected through sequencing with myTYPE.
See this image and copyright information in PMC

References

    1. Manier S, Salem K, Glavey SV, Roccaro AM, Ghobrial IM. Genomic aberrations in multiple myeloma. Cancer Treat. Res. 2016;169:23–34. doi: 10.1007/978-3-319-40320-5_3. - DOI - PubMed
    1. Robiou du Pont S, et al. Genomics of multiple myeloma. J. Clin. Oncol. 2017;35:963–967. doi: 10.1200/JCO.2016.70.6705. - DOI - PubMed
    1. Manier S, et al. Genomic complexity of multiple myeloma and its clinical implications. Nat. Rev. Clin. Oncol. 2017;14:100–113. doi: 10.1038/nrclinonc.2016.122. - DOI - PubMed
    1. Palumbo A, et al. Revised international staging system for multiple myeloma: a report from International Myeloma Working Group. J. Clin. Oncol. 2015;33:2863. doi: 10.1200/JCO.2015.61.2267. - DOI - PMC - PubMed
    1. Bolli N, et al. Analysis of the genomic landscape of multiple myeloma highlights novel prognostic markers and disease subgroups. Leukemia. 2018;32:2604–2616. doi: 10.1038/s41375-018-0037-9. - DOI - PMC - PubMed

Publication types