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SF3B1 mutations and NOTCH1 activation in CLL
84.0% (mean 33.6%) (Online Supplementary Table S1) with 65 canonical c.7541-7542delCT mutations, 35 other trun- cating mutations (nonsense or frameshift), 12 mutations in the 3′-untranslated region and four missense mutations (Figure 1B). Co-occurrence of NOTCH1 and SF3B1 muta- tions was infrequent, being detected in only six cases
A
(1.1%) (Online Supplementary Table S1), suggesting two independent events (c2 P=0.4268) (Online Supplementary Table S2). The remaining 406 cases were unmutated in both genes (wild-type, WT).
TTFT data were available for 382/537 cases: the TTFT intervals for SF3B1-mutated and NOTCH1-mutated cases
B
C
Figure 1. Distributions of mutations in the SF3B1 and NOTCH1 genes and impact on time to first treatment. (A) Distribution of mutations of the SF3B1 gene. The mutated amino acids are indicated and grouped by hotspot. Symbols indicate the different type and number of mutations. The pie chart rep- resents the mutation frequency of each hotspot. (B) Distribution of mutations of the NOTCH1 gene. The mutated amino acids are indicated. Symbols indicate the different type and number of mutations. The pie chart rep- resents the frequency of each mutation type. delCT: c.7541-7542delCT; Ns/Fs: nonsense or frameshift; 3′UTR: 3′ untranslated region; Ms: missense (C) Kaplan-Meier survival analysis for time to first treatment in 382 cases of chronic lymphocytic leukemia with mutations of SF3B1 (n=35), NOTCH1 (n=53) or neither (WT, n=294; P<0.0001 for both comparisons, log-rank test).
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