1. A Next-Generation Sequencing Strategy for Evaluating the Most Common Genetic Abnormalities in Multiple Myeloma.
- Author
-
Jiménez C, Jara-Acevedo M, Corchete LA, Castillo D, Ordóñez GR, Sarasquete ME, Puig N, Martínez-López J, Prieto-Conde MI, García-Álvarez M, Chillón MC, Balanzategui A, Alcoceba M, Oriol A, Rosiñol L, Palomera L, Teruel AI, Lahuerta JJ, Bladé J, Mateos MV, Orfão A, San Miguel JF, González M, Gutiérrez NC, and García-Sanz R
- Subjects
- Aged, Female, Gene Frequency, Genes, Neoplasm, Humans, Male, Middle Aged, Multiple Myeloma diagnosis, Mutation, DNA Mutational Analysis methods, High-Throughput Nucleotide Sequencing methods, Molecular Diagnostic Techniques, Multiple Myeloma genetics
- Abstract
Identification and characterization of genetic alterations are essential for diagnosis of multiple myeloma and may guide therapeutic decisions. Currently, genomic analysis of myeloma to cover the diverse range of alterations with prognostic impact requires fluorescence in situ hybridization (FISH), single nucleotide polymorphism arrays, and sequencing techniques, which are costly and labor intensive and require large numbers of plasma cells. To overcome these limitations, we designed a targeted-capture next-generation sequencing approach for one-step identification of IGH translocations, V(D)J clonal rearrangements, the IgH isotype, and somatic mutations to rapidly identify risk groups and specific targetable molecular lesions. Forty-eight newly diagnosed myeloma patients were tested with the panel, which included IGH and six genes that are recurrently mutated in myeloma: NRAS, KRAS, HRAS, TP53, MYC, and BRAF. We identified 14 of 17 IGH translocations previously detected by FISH and three confirmed translocations not detected by FISH, with the additional advantage of breakpoint identification, which can be used as a target for evaluating minimal residual disease. IgH subclass and V(D)J rearrangements were identified in 77% and 65% of patients, respectively. Mutation analysis revealed the presence of missense protein-coding alterations in at least one of the evaluating genes in 16 of 48 patients (33%). This method may represent a time- and cost-effective diagnostic method for the molecular characterization of multiple myeloma., (Copyright © 2017 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF