The genetic landscape of paediatric de novo acute myeloid leukaemia as defined by single nucleotide polymorphism array and exon sequencing of 100 candidate genes

Cytogenetic analyses of a consecutive series of 67 paediatric (median age 8 years; range 0–17) de novo acute myeloid leukaemia ( AML ) patients revealed aberrations in 55 (82%) cases. The most common subgroups were KMT2A rearrangement (29%), normal karyotype (15%), RUNX1 ‐ RUNX1T1 (10%), deletions of 5q, 7q and/or 17p (9%), myeloid leukaemia associated with Down syndrome (7%), PML ‐ RARA (7%) and CBFB ‐ MYH11 (5%). Single nucleotide polymorphism array ( SNP ‐A) analysis and exon sequencing of 100 genes, performed in 52 and 40 cases, respectively (39 overlapping), revealed ≥1 aberration in 89%; when adding cytogenetic data, this frequency increased to 98%. Uniparental isodisomies ( UPID s) were detected in 13% and copy number aberrations ( CNA s) in 63% (median 2/case); three UPID s and 22 CNA s were recurrent. Twenty‐two genes were targeted by focal CNA s, including AEBP2 and PHF6 deletions and genes involved in AML ‐associated gene fusions. Deep sequencing identified mutations in 65% of cases (median 1/case). In total, 60 mutations were found in 30 genes, primarily those encoding signalling proteins (47%), transcription factors (25%), or epigenetic modifiers (13%). Twelve genes ( BCOR , CEBPA , FLT3 , GATA1 , KIT , KRAS , NOTCH1 , NPM1 , NRAS , PTPN11 , SMC3 and TP53 ) were recurrently mutated. We conclude that SNP ‐A and deep sequencing analyses complement the cytogenetic diagnosis of paediatric AML .