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NGS-Based Molecular Karyotyping of Multiple Myeloma: Results from the GEM12 Clinical Trial

2022; Multidisciplinary Digital Publishing Institute; Volume: 14; Issue: 20 Linguagem: Inglês

10.3390/cancers14205169

2072-6694

Juan Manuel Rosa-Rosa, Isabel Cuenca, Alejandro Medina, Iria Vázquez, Andrea Sánchez-delaCruz, Natalia Buenache, Ricardo Sánchez, Cristina Jiménez, Laura Rosiñol, Norma C. Gutiérrez, Yanira Ruiz‐Heredia, Santiago Barrio, Albert Oriol, María-Luisa Martín-Ramos, María‐Jesús Blanchard, Rosa Ayala, Rafael Ríos, Anna Sureda, Miguel‐Teodoro Hernández, Javier de la Rubia, Gorka Alkorta‐Aranburu, Xabier Agirre, Joan Bladé, María‐Victoria Mateos, Juan José Lahuerta, Jesús F. San Miguel, Marı́a José Calasanz, Ramón García‐Sánz, Joaquín Martínez‐López,

Glycosylation and Glycoproteins Research

Next-generation sequencing (NGS) has greatly improved our ability to detect the genomic aberrations occurring in multiple myeloma (MM); however, its transfer to routine clinical labs and its validation in clinical trials remains to be established. We designed a capture-based NGS targeted panel to identify, in a single assay, known genetic alterations for the prognostic stratification of MM. The NGS panel was designed for the simultaneous study of single nucleotide and copy number variations, insertions and deletions, chromosomal translocations and V(D)J rearrangements. The panel was validated using a cohort of 149 MM patients enrolled in the GEM2012MENOS65 clinical trial. The results showed great global accuracy, with positive and negative predictive values close to 90% when compared with available data from fluorescence in situ hybridization and whole-exome sequencing. While the treatments used in the clinical trial showed high efficacy, patients defined as high-risk by the panel had shorter progression-free survival (p = 0.0015). As expected, the mutational status of TP53 was significant in predicting patient outcomes (p = 0.021). The NGS panel also efficiently detected clonal IGH rearrangements in 81% of patients. In conclusion, molecular karyotyping using a targeted NGS panel can identify relevant prognostic chromosomal abnormalities and translocations for the clinical management of MM patients.