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New Mutations in Chronic Lymphocytic Leukemia Identified by Target Enrichment and Deep Sequencing

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

in Activation / Antigens / B-cell receptor / Biology / Cell cycle / Cell survival / Chronic lymphocytic leukemia / Deoxyribonucleic acid / Disease / DNA / DNA Mutational Analysis / Gene mutation / Gene sequencing / Genes / Genetic aspects / Genomes / High-Throughput Nucleotide Sequencing - methods / Humans / K-Ras protein / Kinases / Leukemia / Leukemia, Lymphocytic, Chronic, B-Cell - genetics / Lung cancer / Lymphatic leukemia / Lymphocytes B / Lymphoma / Medical diagnosis / Medical research / Medicine / Mutant Proteins - genetics / Mutation / Mutation - genetics / Neoplasm Proteins - chemistry / Neoplasm Proteins - genetics / NF-κB protein / Pathology / Pathways / Protein Structure, Tertiary / Proteins / Receptors / Reproducibility of Results / Signaling / T cell receptors / Target recognition / Tumors / Working groups

2012

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New Mutations in Chronic Lymphocytic Leukemia Identified by Target Enrichment and Deep Sequencing

2012

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2012

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Journal Article

New Mutations in Chronic Lymphocytic Leukemia Identified by Target Enrichment and Deep Sequencing

Herreros, Beatriz,

Gómez-Lozano, Natalia,

García-Marco, José A.,

Graña, Osvaldo,

Sánchez-Beato, Margarita,

Gómez-López, Gonzalo,

Gzlez-Peña, Daniel,

López, Mar,

Pisano, David G.,

Menezes, Juliane,

Carro, Angel,

Domínguez, Orlando,

Doménech, Elena,

Piris, Miguel A.

2012

Overview

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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Publisher

Public Library of Science,Public Library of Science (PLoS)

Subject

/ Biology

/ Chronic lymphocytic leukemia