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Background  Pediatric T-cell acute lymphoblastic leukemia (T-ALL) is a genetically heterogeneous disease that arises in a multistep fashion through acquisition of several genetic aberrations, subsequently giving rise to a malignant, clonal expansion of T-lymphoblasts. The aim of the present study was to identify additional as well as cooperative genetic events in T-ALL.    Methods  A population-based pediatric T-ALL series comprising 47 cases was investigated by SNP array and deep sequencing analyses of 75 genes, in order to ascertain pathogenetically pertinent aberrations and to identify cooperative events.    Results  The majority (92%) of cases harbored copy number aberrations/uniparental isodisomies (UPIDs), with a median of three changes (range 0–11) per case. The genes recurrently deleted comprised  CDKN2A ,  CDKN2B ,  LEF1 ,  PTEN ,  RBI , and  STIL . No case had a whole chromosome UPID; in fact, literature data show that this is a rare phenomenon in T-ALL. However, segmental UPIDs (sUPIDs) were seen in 42% of our cases, with most being sUPID9p that always were associated with homozygous  CDKN2A  deletions, with a heterozygous deletion occurring prior to the sUPID9p in all instances. Among the 75 genes sequenced, 14 (19%) were mutated in 28 (72%) of 39 analyzed cases. The genes targeted are involved in signaling transduction, epigenetic regulation, and transcription. In some cases,  NOTCH1  mutations were seen in minor subclones and lost at relapse; thus, such mutations can be secondary events.    Conclusions  Deep sequencing and SNP array analyses of T-ALL revealed lack of wUPIDs, a high proportion of sUPID9p targeting  CDKN2A ,  NOTCH1  mutations in subclones, and recurrent mutations of genes involved in signaling transduction, epigenetic regulation, and transcription.    Electronic supplementary material  The online version of this article (doi:10.1186/s13045-015-0138-0) contains supplementary material, which is available to authorized users.

journal of hematology and oncology

Deep sequencing and SNP array analyses of pediatric T-cell acute lymphoblastic leukemia reveal NOTCH1 mutations in minor subclones and a high incidence of uniparental isodisomies affecting CDKN2A