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Chromosomal aberrations are a hallmark of acute lymphoblastic leukaemia (ALL) but alone fail to induce leukaemia. To identify cooperating oncogenic lesions, we performed a genome-wide analysis of leukaemic cells from 242 paediatric ALL patients using high-resolution, single-nucleotide polymorphism arrays and genomic DNA sequencing. Our analyses revealed(More)
Early T-cell precursor acute lymphoblastic leukaemia (ETP ALL) is an aggressive malignancy of unknown genetic basis. We performed whole-genome sequencing of 12 ETP ALL cases and assessed the frequency of the identified somatic mutations in 94 T-cell acute lymphoblastic leukaemia cases. ETP ALL was characterized by activating mutations in genes regulating(More)
MOTIVATION The occurrence of false positives and false negatives in a microarray analysis could be easily estimated if the distribution of p-values were approximated and then expressed as a mixture of null and alternative densities. Essentially any distribution of p-values can be expressed as such a mixture by extracting a uniform density from it. RESULTS(More)
Pediatric high-grade glioma (HGG) is a devastating disease with a less than 20% survival rate 2 years after diagnosis. We analyzed 127 pediatric HGGs, including diffuse intrinsic pontine gliomas (DIPGs) and non-brainstem HGGs (NBS-HGGs), by whole-genome, whole-exome and/or transcriptome sequencing. We identified recurrent somatic mutations in ACVR1(More)
PURPOSE To conduct a pilot study to determine the safety, feasibility, and engraftment of haploidentical natural killer (NK) cell infusions after an immunosuppressive regimen in children with acute myeloid leukemia (AML). PATIENTS AND METHODS Ten patients (0.7 to 21 years old) who had completed chemotherapy and were in first complete remission of AML were(More)
MOTIVATION Presently available methods that use p-values to estimate or control the false discovery rate (FDR) implicitly assume that p-values are continuously distributed and based on two-sided tests. Therefore, it is difficult to reliably estimate the FDR when p-values are discrete or based on one-sided tests. RESULTS A simple and robust method to(More)
MOTIVATION Recent attempts to account for multiple testing in the analysis of microarray data have focused on controlling the false discovery rate (FDR). However, rigorous control of the FDR at a preselected level is often impractical. Consequently, it has been suggested to use the q-value as an estimate of the proportion of false discoveries among a set of(More)
Medulloblastoma encompasses a collection of clinically and molecularly diverse tumour subtypes that together comprise the most common malignant childhood brain tumour. These tumours are thought to arise within the cerebellum, with approximately 25% originating from granule neuron precursor cells (GNPCs) after aberrant activation of the Sonic Hedgehog(More)
Medulloblastoma is a malignant childhood brain tumour comprising four discrete subgroups. Here, to identify mutations that drive medulloblastoma, we sequenced the entire genomes of 37 tumours and matched normal blood. One-hundred and thirty-six genes harbouring somatic mutations in this discovery set were sequenced in an additional 56 medulloblastomas.(More)
Retinoblastoma is an aggressive childhood cancer of the developing retina that is initiated by the biallelic loss of RB1. Tumours progress very quickly following RB1 inactivation but the underlying mechanism is not known. Here we show that the retinoblastoma genome is stable, but that multiple cancer pathways can be epigenetically deregulated. To identify(More)