New mutations in chronic lymphocytic leukemia identified by target enrichment and deep sequencing.
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.
Molecular Pathology Programme, Spanish National Cancer Research Centre, CNIO, Madrid, Spain.
Elena
E
Doménech
Gonzalo
G
Gómez-López
Daniel
D
Gzlez-Peña
Mar
M
López
Beatriz
B
Herreros
Juliane
J
Menezes
Natalia
N
Gómez-Lozano
Angel
A
Carro
Osvaldo
O
Graña
David G
DG
Pisano
Orlando
O
Domínguez
José A
JA
García-Marco
Miguel A
MA
Piris
Margarita
M
Sánchez-Beato
D004252:DNA Mutational Analysis; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D050505:Mutant Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics; D017434:Protein Structure, Tertiary; D015203:Reproducibility of Results
D050505:Mutant Proteins; D009363:Neoplasm Proteins