Project description:BCR-ABL1 lymphoblastic leukaemia is characterized by the deletion of Ikaros. The Philadelphia chromosome, encoding BCR-ABL1, is the defining lesion of chronic myelogenous leukemia (CML) and a subset of acute lymphoblastic leukemia (ALL) cases. To define oncogenic lesions that cooperate with BCR-ABL1 to induce ALL, we performed genome-wide analysis of leukemic samples from 23 CML cases and 304 ALL cases, including 43 BCR-ABL1 B-ALL cases. IKZF1 (encoding the transcription factor Ikaros) was deleted in 83.7% of BCR-ABL1 B-ALL cases, but not in chronic phase CML. Deletion of IKZF1 was also identified as an acquired lesion in lymphoid blast crisis of CML. The IKZF1 deletions resulted in haploinsufficiency, expression of a dominant negative Ikaros isoform or the complete loss of Ikaros expression. Sequencing of IKZF1 deletion breakpoints suggested that aberrant V(D)J recombination is responsible for the deletions. These findings suggest that genetic lesions resulting in the loss of Ikaros function are a key event in the development of BCR-ABL1 ALL. *** Due to privacy concerns, the primary SNP array data is no longer available with unrestricted access. Individuals wishing to obtain this data for research purposes may request access using the Web links below. *** This SuperSeries is composed of the SubSeries listed below.
Project description:Pediatric patients with de novo acute myeloid leukemia. To define genomic architecture, we performed genome-wide copy number abberation analysis in 460 paired diagnostic-remission bone marrow aspirates.
Project description:Pediatric patients with de novo acute myeloid leukemia. To define genomic architecture, we performed genome-wide copy number abberation analysis in 460 paired diagnostic-remission bone marrow aspirates. Illumina SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic and remission bone marrow samples.
Project description:Acute myeloid leukemia (AML) with t(8;21) and inv(16), together referred as core binding factor (CBF)-AML, are recognized as unique entities. Both rearrangements share a common pathophysiology, the disruption of the CBF, and a relatively good prognosis. Experiments have demonstrated that CBF rearrangements were insufficient to induce leukemia, implying the existence of cooperating events. To explore these aberrations, we performed single nucleotide polymorphism (SNP)-array in a well-annotated cohort of 198 patients with CBF-AML. Excluding breakpoint-associated lesions, the most frequent events included loss of a sex chromosome (53%), deletions at 9q21 (12%) and 7q36 (9%) in patients with t(8;21) compared with trisomy 22 (13%), trisomy 8 (10%) and 7q36 deletions (12%) in patients with inv(16). SNP-array revealed novel recurrent genetic alterations likely to be involved in CBF-AML leukemogenesis. ZBTB7A mutations (20% of t(8;21)-AML) were shown to be a target of copy-neutral losses of heterozygosity (CN-LOH) at chromosome 19p. FOXP1 focal deletions were identified in 5% of inv(16)-AML while sequence analysis revealed that 2% carried FOXP1 truncating mutations. Finally, CCDC26 disruption was found in both subtypes (4.5% of the whole cohort) and possibly highlighted a new lesion associated with aberrant tyrosine kinase signaling in this particular subtype of leukemia.
Project description:Genome-wide profiling of Copy Number Alterations (CNA) and Loss of Heterozygosity (LOH), gene expression and resequencing of pediatric AML. This study characterizes the CNA and LOH in a representative cross-section through subtypes of pediatric AML. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic bone marrow or peripheral blood samples.
Project description:Genome-wide profiling of Copy Number Alterations (CNA) and Loss of Heterozygosity (LOH), gene expression and resequencing of pediatric AML. This study characterizes the CNA and LOH in a representative cross-section through subtypes of pediatric AML. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic bone marrow or peripheral blood samples.
Project description:Genome-wide profiling of Copy Number Alterations (CNA) and Loss of Heterozygosity (LOH), gene expression and resequencing of pediatric AML. This study characterizes the CNA and LOH in a representative cross-section through subtypes of pediatric AML. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic bone marrow or peripheral blood samples.