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H. Larose et al.
Figure 1. Summary of whole exome sequencing data. Individual results for each patient presented as a heatmap for genes found to be mutated in at least a quarter of patients. The number of different variants presenting in each gene is displayed for individual patients. The total number of variants identified for individual patients is also displayed above the graph. The panel on the right shows the percentage of patients presenting with at least one variant of the indicated gene. Pediatric and adult patients are separated. Patients for whom matched peripheral blood was sequenced are labeled with an ‘M’.
NOTCH1 variant T349P provides a growth advantage to cells
Of the 25 ALK+ ALCL tumor samples analyzed by WES, 24% presented with the NOTCH1 variant T349P, while 12% had the T311P variant. These data were validated by Sanger sequencing of a further 78 samples (including 18 of the samples previously analyzed by WES with a total of 55 ALK+ ALCL, and 23 ALK– ALCL) (Online Supplementary Table S2). In this validation cohort, the T349P variant was detected in 12% of patients (n=78;
15% of ALK– patients and 9.3% of ALK+ patients) (Online Supplementary Figure S3A) and the T311P variant was found in 7.6% of patients (n=78; 10.2% of ALK+ patients, none in ALK– patients) (Online Supplementary Figure S3B). In the majority of cases, tumors presented with a muta- tion at either T311P or T349P and therefore the overall incidence of patients with at least one mutation of the EGF-like domain was 18% (n=78), although one patient presented with both mutations. We detected two addi- tional NOTCH1 mutations, H1190P and G1503S,
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