Academic Journal
Molecular profiling of immunoglobulin heavy-chain gene rearrangements unveils new potential prognostic markers for multiple myeloma patients
| Title: | Molecular profiling of immunoglobulin heavy-chain gene rearrangements unveils new potential prognostic markers for multiple myeloma patients |
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| Authors: | Alejandro Medina, Cristina Jiménez, M. Eugenia Sarasquete, Marcos González, M. Carmen Chillón, Ana Balanzategui, Isabel Prieto-Conde, María García-Álvarez, Noemí Puig, Verónica González-Calle, Miguel Alcoceba, Isabel Cuenca, Santiago Barrio, Fernando Escalante, Norma C. Gutiérrez, Mercedes Gironella, Miguel T. Hernández, Anna Sureda, Albert Oriol, Joan Bladé, Juan-José Lahuerta, Jesús F. San Miguel, María-Victoria Mateos, Joaquín Martínez-López, María-José Calasanz, Ramón García-Sanz |
| Contributors: | Repositorio de Navarra, 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, Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72], 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 |
| Source: | Blood Cancer J Blood Cancer Journal r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol instname Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid Consejería de Sanidad de la Comunidad de Madrid Dadun. Depósito Académico Digital de la Universidad de Navarra Universidad de Navarra Dipòsit Digital de la UB Universidad de Barcelona Articles publicats en revistes (Ciències Clíniques) Digital.CSIC. Repositorio Institucional del CSIC Consejo Superior de Investigaciones Científicas (CSIC) Scientia Scientia. Dipòsit d'Informació Digital del Departament de Salut Institut de Recerca Germans Trias i Pujol (IGTP) |
| Publisher Information: | Springer Science and Business Media LLC, 2020. |
| Publication Year: | 2020 |
| Subject Terms: | Adult, Male, 0301 basic medicine, Cèl·lules B, Immunoglobulin Variable Region, PHENOMENA AND PROCESSES::Genetic Phenomena::Gene Expression Regulation::Gene Expression Regulation, Neoplastic, Article, ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de células plasmáticas::mieloma múltiple, 03 medical and health sciences, DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Plasma Cell::Multiple Myeloma, Multiple myeloma, Regulació genètica, Biomarkers, Tumor, Humans, Aged, Aged, 80 and over, Gene Rearrangement, B cells, 0303 health sciences, Gene Expression Profiling, Mieloma múltiple, Middle Aged, Prognosis, 3. Good health, Gene Expression Regulation, Neoplastic, FENÓMENOS Y PROCESOS::fenómenos genéticos::regulación de la expresión génica::regulación de la expresión génica neoplásica, Multigene Family, Female, Immunoglobulin Heavy Chains, Multiple Myeloma, Follow-Up Studies |
| Description: | 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 ofIGHV3,IGHD2andIGHD3, as well asIGHJ4gene 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 ofIGHD2andIGHD3groups were associated with improved prognostic features and longer survival rates in the univariate analyses. Multivariate analysis revealed prolonged progression-free survival rates for patients usingIGHD2/IGHD3groups (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. |
| Document Type: | Article Other literature type |
| File Description: | application/pdf |
| Language: | English |
| ISSN: | 2044-5385 |
| DOI: | 10.1038/s41408-020-0283-8 |
| DOI: | 10.13039/501100000780 |
| DOI: | 10.13039/501100003329 |
| DOI: | 10.13039/501100004587 |
| Access URL: | https://www.nature.com/articles/s41408-020-0283-8.pdf https://pubmed.ncbi.nlm.nih.gov/32029700 https://fundanet.igtp.cat/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=3999 https://hdl.handle.net/20.500.12530/61737 https://hdl.handle.net/10171/67156 http://hdl.handle.net/2445/173319 https://hdl.handle.net/2445/173319 http://hdl.handle.net/10261/222943 https://hdl.handle.net/11351/6280 http://digital.csic.es/bitstream/10261/222943/1/molecpatie.pdf https://europepmc.org/article/MED/32029700 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004993 http://diposit.ub.edu/dspace/bitstream/2445/173319/1/700354.pdf https://www.nature.com/articles/s41408-020-0283-8 https://digital.csic.es/handle/10261/222943 |
| Rights: | CC BY |
| Accession Number: | edsair.doi.dedup.....ab03ff8c3eb2bcb0bc89d89cd65a0f9b |
| Database: | OpenAIRE |
| ISSN: | 20445385 |
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| DOI: | 10.1038/s41408-020-0283-8 |