Comprehensive detection of recurring genomic abnormalities: a targeted sequencing approach for multiple myeloma.
Venkata YellapantulaMalin L HultcrantzEven Holth RustadEster WassermanDory LondonoRobert CimeraAmanda CiardielloHeather LandauTheresia AkhlaghiSham MailankodyMinal PatelJuan Santiago Medina-MartinezJuan Esteban Arango OssaMax Fine LevineNiccolo BolliFrancesco MauraAhmet DoganElli PapaemmanuilYanming ZhangCarl Ola LandgrenPublished in: Blood cancer journal (2019)
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.
Keyphrases
- multiple myeloma
- copy number
- genome wide
- mitochondrial dna
- dna methylation
- clinical trial
- high throughput
- single cell
- label free
- stem cells
- quality improvement
- drug delivery
- single molecule
- study protocol
- transcription factor
- cancer therapy
- living cells
- open label
- fluorescent probe
- circulating tumor cells
- high throughput sequencing