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 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 genes 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. Seven mutated genes (KRAS, SMARCA2, NFKBIE, PRKD3, STAT6, ILB1 and LIFR) have been found and confirmed by capillary sequencing. All of them are present in cases with progressive disease.