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PLoS By Category | Recent PLoS Articles
Hematology

New Mutations in Chronic Lymphocytic Leukemia Identified by Target Enrichment and Deep Sequencing
Published: Friday, June 01, 2012
Author: Elena Doménech et al.

by Elena Doménech, Gonzalo Gómez-López, Daniel Gzlez-Peña, Mar López, Beatriz Herreros, Juliane Menezes, Natalia Gómez-Lozano, Angel Carro, Osvaldo Graña, David G. Pisano, Orlando Domínguez, José A. García-Marco, Miguel A. Piris, Margarita Sánchez-Beato

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.
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