Mutations of Notch1 were identified in 14/210 (6.67%) patients. 13 patient carried a 2bp CT deletion mutation (ΔCT7541-7542, P2489fs*4) and one have GT deletion at 6888-6889bp (V2330Gfs*23). No mutation was identified in the investigated regions of the Notch2 gene.Ten of fourteen (8%) Notch1 mutated sample display an un-mutated V gene and 2 (3.1%) in V gene mutated.

Oncogenic mutations are often associated with the gain or loss of copy number. A copy number variation analysis was performed for Notch-1 and -2 using Applied Biosystem pre-design primer/-probe sets. Samples having confidence values ≥ 0.95 confidence values and ≤ 1.75 Z-score was considered as statistically significant. This analysis revealed the loss of Notch1 allele in 23 samples. Four of Notch1 mutated samples found to carry the loss of allele.

Survival analysis was performed for 210 patients. Overall median survival was 10 years. Univariate survival analysis was done for patients having mutation and loss of copy number in the Notch1 gene. In both cases overall survival (OS) were found significantly decreased (≤5-yr, p<0.05(2a)) compared with the wild type CLL cases (10-yr). Multivariate Cox regression analysis was performed to study the potential mutual effects of loss of copy number and mutation on overall survival. OS were found significantly shorter (<5, p<0.05) when compared to their individual effect. OS were found to be less than 2-yr for the patients carrying both Notch1 mutation and loss of one allele (2c).