Project description:SNP array analysis was performed using 168 ATL specimens. To obtain genotypes and intensities for each SNP, Affymetrix 250K SNP arrays were performed for 168 ATL samples.
Project description:To identify chromosomal alterations in ATL, SNP array analyses were performed in 19 leukemia cell samples from ATL patients and 9 ATL-related cell lines. ATL displayed complex chromosomal abnormalities, but it contained recurrent chromosomal amplification and deletion, including 14q11 and 14q32, which may be associated with the development of ATL. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved peripheral blood samples and from cell line samples.
Project description:We recently mapped 605 chromosomal breakpoints in 61 ATL cases by spectral karyotyping and identified chromosome 14q11 as one of the most common chromosomal breakpoint regions. To map the precise location of chromosomal breakpoints at 14q11, we performed single-nucleotide polymorphism (SNP)-based comparative genomic hybridization on leukemia cells from acute-type ATL patients.
Project description:We recently mapped 605 chromosomal breakpoints in 61 ATL cases by spectral karyotyping and identified chromosome 14q11 as one of the most common chromosomal breakpoint regions. To map the precise location of chromosomal breakpoints at 14q11, we performed single-nucleotide polymorphism (SNP)-based comparative genomic hybridization on leukemia cells from acute-type ATL patients. Copy number analysis of Affymetrix 50K SNP arrays was performed for leukemic cell samples from10 acute-type ATL patients.
Project description:To shed light on the molecular bases of B-lineage acute lymphoblastic leukemia lacking known rearrangements (B-NEG ALL) and the differences between children and adults, we analyzed 168 B-NEG ALLs - including children, adolescents/young adults (AYA) and adults by genome-wide technologies, namely Next-generation sequencing and copy number aberration (CNA). Affymetrix SNP array analysis was performed according to the manufacturer's directions on DNA extracted from bone marrow sampled at diagnosis and paired germline DNA extracted from peripheral blood/bone marrow at complete remission or saliva.
Project description:To shed light on the molecular bases of B-lineage acute lymphoblastic leukemia lacking known rearrangements (B-NEG ALL) and the differences between children and adults, we analyzed 168 B-NEG ALLs - including children, adolescents/young adults (AYA) and adults by genome-wide technologies, namely Next-generation sequencing and copy number aberration (CNA). Affymetrix SNP array analysis was performed according to the manufacturer's directions on DNA extracted from bone marrow sampled at diagnosis and paired germline DNA extracted from peripheral blood/bone marrow at complete remission or saliva. Copy number analysis of Affymetrix SNP 6.0 arrays was performed for 13 B-NEG ALL samples and their paired normal (non-tumoral) DNA samples, included in the discovery panel, processed in the same experiment and deposited.
Project description:Abstract: Adult T-cell leukemia/lymphoma (ATL) is an aggressive and fatal disease. We have examined 18 ATL patient samples using Affymetrix HG-U133A2.0 arrays. Using the BRB array program, we identified genes differentially expressed in leukemia cells compared to normal lymphocytes. Several unique genes were identified that were overexpressed in leukemia cells including TNFSF11, RGS13, MAFb, CSPG2, C/EBPalpha and TCF4. 200 of the most highly overexpressed ATL genes were analyzed by the PathwayStudio 4.0 program. ATL leukemia cells were characterized by an increase in genes linked to "central" genes CDC2/cyclin B1, SYK/LYN, PCNA and BIRC5. Because of its potential therapeutic importance, we focused our studies on the regulation and function of BIRC5, whose expression was increased in 13 of 14 leukemia samples. TCF4 reporter assays and transfection of DN-TCF4 demonstrated that TCF4 regulates BIRC5 gene expression. Functionally, transfection of ATL cells wi BIRC5 shRNA decreased BIRC5 exprression and cell viability 80%. Clinical treatment of ATL patients with Zenapax or bortezomib decreased BIRC5 expression and cell viability. These experiments represent the first direct experimental evidence that BIRC5 plays an important role in ATL cell viability and provides important insight into ATL genesis and potential targeted therapies. Experiment Overall Design: Gene expression profiles of 7 control and 18 ATL patient samples were analyzed using Affymetrix HG-U133A2.0 arrays.
Project description:We recently mapped 605 chromosomal breakpoints in 61 ATL cases by spectral karyotyping and identified chromosome 14q11 as one of the most common chromosomal breakpoint regions. To map the precise location of chromosomal breakpoints at 14q11, we performed single-nucleotide polymorphism (SNP)-based comparative genomic hybridization on leukemia cells from acute-type ATL patients. The breakpoints accumulated frequently adjacent to the T cell receptor alpha/delta chain locus (TCRα/δ) with chromosomal deletions at 14q11 and a recurrent 0.9 Mb interstitial deletion was identified at a region including part of the TCRα/δ locus. Because leukemia-associated genes are frequently located near the breakpoint cluster regions, we then analyzed the gene expression profiles of ATL cells and identified N-myc downstream regulated gene 2 (NDRG2) as one of the genes that are down-regulated in ATLL cells among the 25 genes mapped to the region adjacent to the recurrently deleted regions at 14q11. We compared the gene expression profiles of ATL cells from seven acute-type ATL patients and CD4+ T lymphocytes from the peripheral blood of five healthy volunteers as references using oligonucleotide microarrays.
Project description:allele call files from analysis of NCI60 cell line DNA on 100K SNP arrays. Keywords = NCI60, SNP array, cancer cell line Keywords: other
Project description:Single nucleotide polymorphism (SNP) microarrays are commonly applied to tumors to identify genomic regions with copy number alterations (CNA) or loss of heterozygosity (LOH). However, in typical tumor specimens collected in clinical studies, up to 60% of the DNA derives from stromal cells with a normal genome, resulting in attenuated sensitivity to true somatic aberrations in the tumor. Here we describe SNPfilter, a model-based method to decompose SNP array data from heterogeneous tumor specimens into their corresponding normal and tumor profiles. Unlike existing methods, SNPfilter does not require paired normal control data. We assessed the performance of this method using SNP array data representing cancer cell lines with aberrant genomes, B-cell lymphoblastoid cell lines with normal genomes, and defined mixtures of the two. In the pure tumor samples, SNPfilter identified CNA and LOH regions with accuracy similar to existing methods. In the mixture samples containing 40–80% tumor genomic DNA, SNPfilter yielded prediction sensitivity superior to existing methods. Thus, SNPfilter provides a powerful tool for discovery of clinically relevant somatic aberrations in tumor genomes.