Integrative Analysis of a series of newly diagnosed Diffuse Large B-cell Lymphomas (DLBCLs)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE34171 | GEO | 2012/09/12
SECONDARY ACCESSION(S): PRJNA149723
REPOSITORIES: GEO
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Project description:Diffuse large B-cell lymphoma (DLBCL) is a clinically and biologically heterogeneous disease. We have characterized recurrent copy number alterations (CNAs) in a large series of primary DLBCLs with HD-SNP arrays and the GISTIC algromithm. We evaluated the associations between transcript abundance and the presence of specific CNAs by obtaining RNA profiles on the majority of the primary DLBCLs and integrating the gene expression profiles with the copy number data. High molecular weight DNA and total RNA were extracted from frozen biopsy specimens of newly diagnosed and previously untreated primary DLBCLs according to IRB-approved protocols. DLBCL diagnoses and > 80% tumor involvement were confirmed by expert hematologists. 180 primary DLBCLs and 53 normal DNA samples were profiled on Affymetrix SNP array 6.0. 169 of these primary DLBCLs were RNA profiled, 78 on Affymetrix U133A+B and 91 on U133plus2 arrays.
2012-09-12 | E-GEOD-34171 | biostudies-arrayexpress
Project description:Frozen biopsies collected at diagnosis from 51 DLBCLs were analyzed to find recurrent copy number events in this disease. Hybridizations were performed against a common DNA pool.
2017-05-15 | E-MTAB-4497 | biostudies-arrayexpress
Project description:Frozen biopsies collected at diagnosis from 38 DLBCLs were analyzed to find recurrent copy number events in this disease. Hybridizations were performed against matching DNA samples extracted from Peripheral Blood Mononuclear Cells (PBMC).
2017-05-15 | E-MTAB-4495 | biostudies-arrayexpress
Project description:Frozen biopsies collected at diagnosis from 18 DLBCLs were analyzed to find copy number events that could predict the relapse. Hybridizations were performed against a common DNA pool.
2017-05-15 | E-MTAB-4496 | biostudies-arrayexpress
Project description:84 NSCLC cell lines were collected from various sources (Supplemental Table 1) and formed the basis for all subsequent experiments. Cell lines were derived from tumors representing all major subtypes of NSCLC tumors, including adenocarcinoma, squamous-cell carcinoma and large-cell carcinoma. The genomic landscape of these cell lines was characterized by analyzing gene copy number alterations using high-resolution single-nucleotide polymorphism (SNP) arrays (250K Sty1). We used the statistical algorithm Genomic Identification of Significant Targets in Cancer (GISTIC) to distinguish biologically relevant lesions from background noise. The application of GISTIC revealed 16 regions of recurrent, high-level copy number gain (inferred copy number > 2.14) and 20 regions of recurrent copy number loss (inferred copy number < 1.86)
2009-07-29 | GSE17247 | GEO
Project description:Genomic abnormalities leading to colorectal cancer (CRC) include somatic events causing copy number aberrations (CNAs) as well as copy neutral manifestations such as loss of heterozygosity (LOH) and uniparental disomy (UPD). We studied the causal effect of these events by analyzing high resolution cytogenetic microarray data of 15 tumor-normal paired samples. We detected 144 genes affected by CNAs. A subset of 91 genes are known to be CRC related yet high GISTIC scores indicate 24 genes on chromosomes 7, 8, 18 and 20 to be strongly relevant. Combining GISTIC ranking with functional analyses and degree of loss/gain we identify three genes in regions of significant loss (ATP8B1, NARS, and ATP5A1) and eight in regions of gain (CTCFL, SPO11, ZNF217, PLEKHA8, HOXA3, GPNMB, IGF2BP3 and PCAT1) as novel in their association with CRC. Pathway analysis indicates TGF-β signaling pathway to be affected by the cytogenetic events causing CRC as evidenced by the action of genes impacted by CNAs on SMAD family of proteins. Finally, LOH and UPD collectively affected nine cancer related genes. Transcription factor binding sites on regions of >35% copy number loss/gain influenced 16 CRC genes. Our analysis shows patient specific CRC manifestations at the genomic level and that these different events affect individual CRC patients differently.
2013-09-01 | GSE47204 | GEO
Project description:Genomic abnormalities leading to colorectal cancer (CRC) include somatic events causing copy number aberrations (CNAs) as well as copy neutral manifestations such as loss of heterozygosity (LOH) and uniparental disomy (UPD). We studied the causal effect of these events by analyzing high resolution cytogenetic microarray data of 15 tumor-normal paired samples. We detected 144 genes affected by CNAs. A subset of 91 genes are known to be CRC related yet high GISTIC scores indicate 24 genes on chromosomes 7, 8, 18 and 20 to be strongly relevant. Combining GISTIC ranking with functional analyses and degree of loss/gain we identify three genes in regions of significant loss (ATP8B1, NARS, and ATP5A1) and eight in regions of gain (CTCFL, SPO11, ZNF217, PLEKHA8, HOXA3, GPNMB, IGF2BP3 and PCAT1) as novel in their association with CRC. Pathway analysis indicates TGF-β signaling pathway to be affected by the cytogenetic events causing CRC as evidenced by the action of genes impacted by CNAs on SMAD family of proteins. Finally, LOH and UPD collectively affected nine cancer related genes. Transcription factor binding sites on regions of >35% copy number loss/gain influenced 16 CRC genes. Our analysis shows patient specific CRC manifestations at the genomic level and that these different events affect individual CRC patients differently. Copy number analysis of Affymetrix CytoScanHD arrays was performed for 15 Tumors and 15 Adjacent Normals from Colorectal Tissue was used as reference for the study.
2013-09-01 | E-GEOD-47204 | biostudies-arrayexpress
Project description:<p>Diffuse large B-cell lymphoma (DLBCL), the most common lymphoid malignancy in adults, is a clinically and genetically heterogenous disease that is further classified into transcriptionally defined activated B-cell (ABC) and germinal center B-cell (GCB) subtypes. Here, we describe a comprehensive genetic analysis of DLBCLs that identifies low-frequency alterations, captures recurrent mutations, copy number alterations (CNAs) and structural variants (SVs) and characterizes coordinate genetic signatures in 304 primary DLBCLs with available outcome data. We integrated these genetic drivers using consensus clustering and identified 5 robust DLBCL subsets, including a previously unrecognized group of low-risk ABC-DLBCLs of extrafollicular/marginal zone origin; 2 distinct subsets of GCB-DLBCLs with different outcomes and targetable alterations; and an ABC/GCB-independent group with biallelic inactivation of TP53, CDKN2A loss and associated genomic instability. The genetic features of the newly identified subsets, their mutational signatures and the temporal ordering of identified alterations provide new insights into DLBCL pathogenesis. The coordinate genetic signatures also predict outcome independent of the clinical International Prognostic Index and suggest new combination treatment strategies. More broadly, these studies provide a roadmap for an actionable DLBCL classification. </p>
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Project description:Large but not small copy-number alterations correlate to high-risk genomic aberrations and survival in chronic lymphocytic leukemia: a high-resolution genomic screening of newly diagnosed patients. Single nucleotide polymorphism (SNP)-arrays allow simultaneous detection of copy-number aberrations (CNAs) and copy-number neutral loss-of-heterozygosity (CNN-LOH). In this study we investigated the presence of CNAs and CNN-LOH in newly diagnosed CLL samples from a Swedish chronic lymphocytic leukemia (CLL) cohort. In this study we could detect the known recurrent aberrations in CLL (i.e. deletions of 13q, 11q, 17p and trisomy 12). We also detected other both large and small CNAs which were mostly non-recurrent. CNN-LOH was detected on chromosome 13q in patients that carried homozygous deletion of 13q.
2009-11-23 | GSE16406 | GEO
Project description:In order to screen potential novel 'driver genes' in lung cancer in Xuanwei (LCXW), genome-wide DNA copy number alterations (CNAs) were detected on 8 paired LCXW and non-cancerous lung (NCL) tissues by array-based comparative genomic hybridization microarrays. The log2 copy-number ratio calculation and CNA calls were determined using segMNT algorithm in NimbleScan. Log2 ratio test/control thresholds of 0.25 and -0.25 were defined as copy number gains and losses, respectively. Deviant signal intensity ratios involving 5 or more neighboring probes were considered as genomic aberrations. A large number of CNAs and DEGs were detected, respectively. Many recurrent CNAs were screened out, including gains at 5p15.33-p15.32, 5p15.1-p14.3 and 5p14.3-p14.2, and losses at 11q24.3, 21q21.1, 21q22.12-q22.13 and 21q22.2.
2016-10-22 | GSE89046 | GEO