acute myeloid leukemia reveals new recurrent genomic alterations High-resolution genomic profiling of adult and pediatric core-binding-factor

ABSTRACT To identify cooperating lesions in core-binding factor acute myeloid leukemia (CBF-AML), we performed single-nucleotide polymorphism (SNP)-array analysis on 300 diagnostic and 41 relapse adult and pediatric leukemia samples. We identified a mean of 1.28 copy number alterations (CNAs) per case at diagnosis in both patient populations. Recurrent minimally deleted regions (MDR) were identified at 7q36.1 (7.7%), 9q21.32 (5%), 11p13 (2.3%), and 17q11.2 (2%). About half of the 7q deletions were detectable only by SNP-array analysis because of their limited size. Sequence analysis of MLL3, contained within the 7q36.1 MDR, in 46 diagnostic samples revealed one truncating mutation in a leukemia lacking a 7q deletion. Recurrent focal gains were identified at 8q24.21 (4.7%) and 11q25 (1.7%), both containing a single non-coding RNA. Recurrent regions of copy-neutral loss-of-heterozygosity were identified at 1p (1%), 4q (0.7%), and 19p (0.7%) with known mutated cancer genes present in the minimally altered region of 1p (

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