New mutations in chronic lymphocytic leukemia identified by target enrichment and deep sequencing
| Autor: | Mar Lopez, Beatriz Herreros, Gonzalo Gómez-López, Angel Carro, José A. García-Marco, Orlando Domínguez, David G. Pisano, Natalia Gómez-Lozano, Daniel Gzlez-Peña, Osvaldo Graña, Juliane Menezes, Miguel A. Piris, Margarita Sánchez-Beato, Elena Domenech |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Chronic lymphocytic leukemia
Science DNA Mutational Analysis Biology medicine.disease_cause Deep sequencing Germline mutation hemic and lymphatic diseases Leukemias Genetics Cancer Genetics medicine Humans Genome Sequencing Non-Hodgkin lymphoma Chronic Lymphoblastic Leukemia Mutation Multidisciplinary Massive parallel sequencing breakpoint cluster region High-Throughput Nucleotide Sequencing Reproducibility of Results Computational Biology Genomics Hematology medicine.disease Leukemia Lymphocytic Chronic B-Cell NFKBIE Neoplasm Proteins Protein Structure Tertiary Hematologic cancers and related disorders Cancer research Medicine Mutant Proteins Lymphomas Sequence Analysis Research Article |
| Zdroj: | PLoS ONE, Vol 7, Iss 6, p e38158 (2012) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Chronic lymphocytic leukemia (CLL) is a heterogeneous disease without a well-defined genetic alteration responsible for the onset of the disease. Several lines of evidence coincide in identifying stimulatory and growth signals delivered by B-cell receptor (BCR), and co-receptors together with NFkB pathway, as being the driving force in B-cell survival in CLL. However, the molecular mechanism responsible for this activation has not been identified. Based on the hypothesis that BCR activation may depend on somatic mutations of the BCR and related pathways we have performed a complete mutational screening of 301 selected genes associated with BCR signaling and related pathways using massive parallel sequencing technology in 10 CLL cases. Four mutated genes in coding regions (KRAS, SMARCA2, NFKBIE and PRKD3) have been confirmed by capillary sequencing. In conclusion, this study identifies new genes mutated in CLL, all of them in cases with progressive disease, and demonstrates that next-generation sequencing technologies applied to selected genes or pathways of interest are powerful tools for identifying novel mutational changes. |
| Databáze: | OpenAIRE |
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