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Pàgina inicial > Articles > Articles publicats > Integrating genomic alterations in diffuse large B-cell lymphoma identifies new relevant pathways and potential therapeutic targets |
Data: | 2018 |
Resum: | Genome studies of diffuse large B-cell lymphoma (DLBCL) have revealed a large number of somatic mutations and structural alterations. However, the clinical significance of these alterations is still not well defined. In this study, we have integrated the analysis of targeted next-generation sequencing of 106 genes and genomic copy number alterations (CNA) in 150 DLBCL. The clinically significant findings were validated in an independent cohort of 111 patients. Germinal center B-cell and activated B-cell DLBCL had a differential profile of mutations, altered pathogenic pathways and CNA. Mutations in genes of the NOTCH pathway and tumor suppressor genes (TP53/CDKN2A), but not individual genes, conferred an unfavorable prognosis, confirmed in the independent validation cohort. A gene expression profiling analysis showed that tumors with NOTCH pathway mutations had a significant modulation of downstream target genes, emphasizing the relevance of this pathway in DLBCL. An in silico drug discovery analysis recognized 69 (46%) cases carrying at least one genomic alteration considered a potential target of drug response according to early clinical trials or preclinical assays in DLBCL or other lymphomas. In conclusion, this study identifies relevant pathways and mutated genes in DLBCL and recognizes potential targets for new intervention strategies. |
Ajuts: | Ministerio de Economía y Competitividad SAF2015-64885-R Ministerio de Economía y Competitividad PI12/01536 Ministerio de Economía y Competitividad PI16/00420 Ministerio de Economía y Competitividad RD12/0036/0036 Ministerio de Economía y Competitividad RD12/0036/0023 Ministerio de Economía y Competitividad RD12/0036/0069 Ministerio de Economía y Competitividad SAF2015-74072-JIN |
Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. |
Llengua: | Anglès |
Document: | Article ; recerca ; Versió publicada |
Publicat a: | Leukemia, Vol. 32 Núm. 3 (january 2018) , p. 675-684, ISSN 1476-5551 |
10 p, 2.0 MB |