Affymetrix SNP array data for acute lymphoblastic leukemia samples
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ABSTRACT: Development of B-acute lymphoblastic leukemia accompanies with multiple variable mutations. Beside the structural and chromosomal alterations, especially mutations in the regulators of B cell differentiation are common. Around 60% of the B-ALL show deletions of these genes. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic bone marrow or peripheral blood samples. Copy number analysis of Affymetrix SNP 6.0 arrays was performed for 20 pediatric B-ALL samples and intraindividually matching remission samples which were used as references.
Project description:DNA copy number alterations and mutations were characterised by bulk SNP anlaysis and exome sequencing (not sown here) in three acute lymphoblastic leukaemia samples and one establish cell line REH. Further single cell experiments of these cases investigated the mutation and copy number targets previously defined exploring the sub-clonal populations and phylogenic trees within each leukaemia. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic bone marrow or peripheral blood samples. Copy number analysis of Affymetrix SNP6 arrays or Cytogenetics whole genome 2.7M arrays was performed for three leukaemic samples and one established cell line REH. Remission samples were only available for two of the leukaemia samples (Case A and Case B) and therefore 20 HapMap Caucasien samples were used as controls for the SNP6 array expeeriments.
Project description:Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved HNSCC samples. Copy number analysis of Affymetrix 500K SNP arrays was performed for 11 HNSCC samples, which were used as references for copy number inference.
Project description:Transient abnormal myelopoiesis (TAM) is a clonal pre-leukemic disorder that progresses to myeloid leukemia of Down syndrome (ML-DS) through the accumulation of genetic alterations. To investigate the mechanism of leukemogenesis in this disorder, a xenograft model of TAM was established using NOD/Shi-scid, IL-2Rγnull mice. In serial transplantations, engrafted TAM-derived cells showed the emergence of divergent subclones with another GATA1 mutation and various CNAs, including a 16q deletion and 1q gain, which are clinically associated with ML-DS. These results suggest that genetically heterogeneous subclones with varying leukemia-initiating potential already exist in the neonatal TAM phase, and ML-DS may develop from a pool of such minor clones through clonal selection. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from murine bone marrow (hCD45 sorted) or human peripheral blood samples. Copy number analysis of Affymetrix 500K SNP arrays was performed for xenografted TAM samples of 3 patients. There are also 3 samples from TAM patients in remission, which were used as references for copy number inference.
Project description:Although in 80% of CLL cases that require therapy is possible to achieve a complete remission using a combination of fludarabine, anti-CD20 in conjunction with cyclophosphamide and/or mitoxantrone, 20% of patients do not achieve disease control with this conventional approach. The main reason of complete remission failure is chemorefractoriness to fludarabine that occurs in up to 10% of patients requiring treatment. In order to identify new molecular predictors of refractoriness as well as druggable therapeutic targets, we combined next-generation sequencing and copy number analyses. Affymetrix SNP array analysis was performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic samples. Copy number analysis of Affymetrix SNP 6.0 arrays was performed for 10 FR-CLL samples and their paired normal (non-tumoral) DNA samples, processed in the same experiment and deposited (discovery set). The analysis was then extended to 29 additional FR-CLL tumoral samples and 3 Normal DNAs processed in the same experiment, including the Reference Normal DNA provided by Affymetrix (screening set).
Project description:To identify genomic alterations in chronic lymphocytic leukemia (CLL), we performed single-nucleotide polymorphism (SNP)-array analysis on 353 samples from previously untreated patients entered on the CLL8 treatment trial. Based on paired-sample analysis (n=147), a mean of 1.8 copy number alterations (CNAs) per case were identified; about 60% of cases carried no CNAs other than those detected by routine fluorescence in-situ hybridization analysis. Copy-neutral loss-of- heterozygosity was detected in 6% of cases, and most frequently found on 13q, 17p and 11q. Minimal deleted regions (MDRs) were refined on 13q14 (deleted in 61% of cases) to the DLEU1 and DLEU2 genes, on 11q22.3 (27%) to ATM, on 2p (gained in 7% of cases) to a 1.9 Mb fragment containing 9 genes, and on 8q24 (5%) to a segment 486 Kb proximal of the MYC locus. 13q deletions exhibited proximal and distal breakpoint cluster regions. Among the most common novel lesions were deletions at 15q15.1 (4%), with the smallest deletion (70.5 Kb) found in the MGA locus; sequence analysis of MGA in 59 samples revealed a truncating mutation in one case lacking a 15q deletion. MNT at 17p13.3, which in addition to MGA and MYC encodes for the network of MAX-interacting proteins, was also found recurrently deleted. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic peripheral blood samples. Copy number analysis of Affymetrix® performed for 353 CLL samples. There are also 147 samples from mononuclear cells negative for CD19, which were used as references for copy number inference.
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:Development of B-acute lymphoblastic leukemia accompanies with multiple variable mutations. Beside the structural and chromosomal alterations, especially mutations in the regulators of B cell differentiation are common. Around 60% of the B-ALL show deletions of these genes.
Project description:SNP profiling can reveal copy number abnormalities and loss of heterozygosity associated with distinct biologic subtypes of acute lymphoblastic leukemia (ALL). We performed SNP profiling of Down syndrome ALL cases and controls to identify unique biologic features of this ALL subgroup. Ficoll-enriched, cryopreserved bone marrow aspirate samples were obtained from patients with B-precursor ALL at diagnosis and in remission; and from control patients without leukemia.
Project description:Analysis of the molecular etiologies of severe combined immunodeficiency (SCID) has led to important insights into the control of immune cell development. Most cases of SCID result from either X-linked or autosomal recessive inheritance of mutations in a known causative gene. However, in some cases, the molecular etiology remains unclear. To identify the cause of SCID in a patient known to lack the protein tyrosine phosphatase CD45, we utilized single nucleotide polymorphisms (SNP) Cytogenetics arrays; The patient’s mother was heterozygous for an inactivating mutation in CD45, while the paternal alleles exhibited no detectable mutations. The patient exhibited a single CD45 mutation identical to the maternal allele. Patient SNP array analysis revealed no change in copy number but loss of heterozygosity for the entire length of chromosome 1 (Chr1), indicating that disease was caused by uniparental disomy (UPD) with isodisomy of the entire maternal Chr1 bearing the mutant CD45 allele. Non-lymphoid blood cells and other mesoderm and ectoderm-derived tissues retained UPD of the entire maternal Chr1 in this patient who had undergone successful bone marrow transplantation. These findings represent the first reported case of SCID caused by UPD and suggest UPD should be considered in SCID and other recessive disorders, especially when the patient appears homozygous for an abnormal gene found in only one parent. Evaluation for alterations in other genes affected by UPD should also be considered in such cases. Affymetrix SNP Cytogenetics arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved sorted PMBC and buccal samples. Copy number and allele analysis of Affymetrix Cytogenetics arrays was performed for the patient's and his parent's samples.
Project description:DNA from four 29 cases, 38 tumor samples (23 PB, 12 LN, 1 Tonsil, 1 colonic biopsy, 1 spleen) and 29 normal DNA from the same patients were analyzed with Affymetrix SNP 6.0 platform for copy number alterations study. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from blood samples, lymph nodes and other tissues like spleen, tonsil and colonic biopsy Copy number analysis of Affymetrix SNP 6.0 arrays was performed for 29 MCL cases samples and their respective matched non-tumor DNA, which were used as references for copy number inference.