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Title: NGS-Based Molecular Karyotyping of Multiple Myeloma: Results from the GEM12 Clinical Trial
Author: Rosa Rosa, Juan Manuel
Cuenca, Isabel
Medina, Alejandro
Vázquez, Iria
Sánchez de la Cruz, Andrea
Buenache, Natalia
Sánchez, Ricardo
Jiménez, Cristina
Rosiñol, Laura
Gutiérrez, Norma C.
Ruiz Heredia, Yanira
Barrio, Santiago
Oriol, Albert
Martin Ramos, Maria Luisa
Blanchard, María Jesús
Ayala, Rosa
Ríos Tamayo, Rafael
Sureda, Anna
Hernández, Miguel Teodoro
Rubia, Javier de la
Alkorta Aranburu, Gorka
Agirre, Xabier
Bladé, J. (Joan)
Mateos, María Victoria
Lahuerta, Juan José
San Miguel, Jesús F.
Calasanz, María José
Garcia Sanz, Ramon
Martínez López, Joaquín
Keywords: Citogenètica
Mieloma múltiple
Multiple myeloma
Issue Date: 21-Oct-2022
Publisher: MDPI AG
Abstract: Simple Summary Multiple Myeloma (MM) is considered an incurable chronic disease, which prognosis depends on the presence of different genomic alterations. To accomplish a complete molecular diagnosis in a single essay, we have designed and validated a capture-based NGS approach to reliably identify pathogenic mutations (SNVs and indels), genomic alterations (CNVs and chromosomic translocations), and IGH rearrangements. We have observed a good correlation of the results obtained using our capture panel with data obtained by both FISH and WES techniques. In this study, the molecular classification performed using our approach was significantly associated with the stratification and outcome of MM patients. Additionally, this panel has been proven to detect specific IGH rearrangements that could be used as biomarkers in patient follow-ups through minimal residual disease (MRD) assays. In conclusion, we think that MM patients could benefit from the use of this capture-based NGS approach with a more accurate, single-essay molecular diagnosis. 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.
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It is part of: Cancers, 2022, vol. 14, num. 20
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ISSN: 2072-6694
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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