and FLT3, NF1, NRAS, SETD2 (2/20); by panel sequencing only TP53, FLT3 and RAS-pathway genes
were recurrently mutated.
Conclusions: The simultaneous analysis of chromosome aneuploidy, structural variants, gene
mutations and transcriptional profiles by WGS-WTS is highly valuable in differentiating genetically
distinct B-ALL subgroups. This approach identified defining events in 18 of 20 patients, and may
overcome recognised limitations of conventional cytogenetics contributing to false-negatives
(observed in 9 of 20 patients) including cryptic rearrangements, copy neutral abnormalities and sub-optimal
chromosome morphology. Routine DNA-based targeted panels will identify TP53 mutated
cases (a surrogate for low hypodiploid), but may not be adequately designed to detect other driver
events in B-ALL. Conversely, WGS analysis can be easily adapted as optimal gene panels are
established.
