Molecular profiling of immunoglobulin heavy-chain gene rearrangements unveils new potential prognostic markers for multiple myeloma patients
| Autor: | Medina, Alejandro, Jiménez, C., Sarasquete, M. E., González, M., Chillón, M. Carmen, Balanzategui, A., Prieto-Conde, I., García-Álvarez, M., Puig, N., González-Calle, Verónica, Alcoceba, Miguel, Cuenca, I., Barrio, S., Escalante, F., Gutiérrez, N. C., Gironella, Mercedes, Hernández, M. T., Sureda, A., Oriol, Albert, Bladé Creixenti, Juan, Lahuerta, J. J., San Miguel, J. F., Mateos, M. V., Martínez-López, J., Calasanz, M.J, García-Sanz, Ramón, Universitat Autònoma de Barcelona |
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| Přispěvatelé: | Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Fundación CRIS contra el Cáncer, Fundacion de la Sociedad Española de Hematología y Hemoterapia, Universidad de Salamanca, European Commission, Institut Català de la Salut, [Medina A, Jiménez C, Sarasquete ME, González M, Chillón MC, Balanzategui A] Hospital Universitario de Salamanca (HUSAL), IBSAL, IBMCC (USAL-CSIC), CIBERONC, Salamanca, Spain. [Gironella M] Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus |
| Rok vydání: | 2020 |
| Předmět: |
Oncology
Male Immunoglobulin Variable Region Myeloma Disease fenómenos genéticos::regulación de la expresión génica::regulación de la expresión génica neoplásica [FENÓMENOS Y PROCESOS] Pathogenesis Multiple myeloma Genetics research Aged 80 and over Gene Rearrangement Univariate analysis biology Neoplasms::Neoplasms by Histologic Type::Neoplasms Plasma Cell::Multiple Myeloma [DISEASES] Hematology Middle Aged Prognosis lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Gene Expression Regulation Neoplastic Multigene Family Female Antibody Immunoglobulin Heavy Chains Multiple Myeloma Adult medicine.medical_specialty Cèl·lules B Genetic Phenomena::Gene Expression Regulation::Gene Expression Regulation Neoplastic [PHENOMENA AND PROCESSES] Somatic hypermutation lcsh:RC254-282 Article Internal medicine Regulació genètica medicine Biomarkers Tumor Humans neoplasias::neoplasias por tipo histológico::neoplasias de células plasmáticas::mieloma múltiple [ENFERMEDADES] Gene Aged B cells business.industry Gene Expression Profiling Mieloma múltiple medicine.disease Transplantation biology.protein business Follow-Up Studies |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname Scientia Blood Cancer Journal r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona Dipòsit Digital de la UB Universidad de Barcelona Blood Cancer Journal, Vol 10, Iss 2, Pp 1-12 (2020) |
| ISSN: | 2044-5385 |
| Popis: | Multiple myeloma is a heterogeneous disease whose pathogenesis has not been completely elucidated. Although B-cell receptors play a crucial role in myeloma pathogenesis, the impact of clonal immunoglobulin heavy-chain features in the outcome has not been extensively explored. Here we present the characterization of complete heavy-chain gene rearrangements in 413 myeloma patients treated in Spanish trials, including 113 patients characterized by next-generation sequencing. Compared to the normal B-cell repertoire, gene selection was biased in myeloma, with significant overrepresentation of IGHV3, IGHD2 and IGHD3, as well as IGHJ4 gene groups. Hypermutation was high in our patients (median: 8.8%). Interestingly, regarding patients who are not candidates for transplantation, a high hypermutation rate (≥7%) and the use of IGHD2 and IGHD3 groups were associated with improved prognostic features and longer survival rates in the univariate analyses. Multivariate analysis revealed prolonged progression-free survival rates for patients using IGHD2/IGHD3 groups (HR: 0.552, 95% CI: 0.361−0.845, p = 0.006), as well as prolonged overall survival rates for patients with hypermutation ≥7% (HR: 0.291, 95% CI: 0.137−0.618, p = 0.001). Our results provide new insights into the molecular characterization of multiple myeloma, highlighting the need to evaluate some of these clonal rearrangement characteristics as new potential prognostic markers. This work was partially supported by the Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness PI15/01956, CIBERONC-CB16/12/00233, and “Una manera de hacer Europa” (Innocampus; CEI-2010-1-0010)”. M.G.-A., I.P.-C., and C.J. are supported by the Fundación Española de Hematología y Hemoterapia (FEHH, co-funded by Fundación Cris in the latter case), A.M. by the European Social Fund and the Spanish Education Council through the University of Salamanca, and M.E.S. by the ISCIII (CPII18/00028). All Spanish funding is co-sponsored by the European Union FEDER program. |
| Databáze: | OpenAIRE |
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