MATERIALS AND METHODS: Whole genome sequencing was performed on matched samples collected at diagnosis, remission and relapse from three patients of de novo childhood AML. Sanger sequencing was performed for validation in 47 patients' samples, followed by functional analysis.

RESULTS: Overall, we identified 312 somatic mutations including synonymous single nucleotide variants (SNVs), missense SNVs, deletions and insertion frameshifts, stopgains and splice sites. After prioritisation, only 46 variants were present at diagnosis (13-17 mutations per patient) and 49 variants at relapse (12-20 mutations per patient). Out of 81 variants, there were 35 new variants detected at relapse but not present at diagnosis. Six potential driver mutations (KIT, CDC73, HNF1A, RBM10, ZMYM4 and ETV6) were identified in predicting relapse for the 3 patients, with recurrent mutations of the ETV6 gene in 2 patients. Functional analysis of the ETV6 mutation showed that ETV6 lost its tumour suppressive function when both mutant ETV6 p.P25fs and ETV6 p.N75fs were tested in vitro.