Project description:With the whole genome SNPs array information, we could evaluate the copy number variation of samples so as to find out specific DNA aberrations in non-Hodgkin lymphma comparing with reactive hyperplasia patients.
Project description:This SuperSeries is composed of the following subset Series: GSE25986: Gene expression profiling of cell lines derived from classical Hodgkin lymphoma GSE25987: Gene expression profiling of Hodgkin lymphoma cell line KMH2: Comparison of CIITA-BX648577 knockdown cultures with non-silencing controls GSE25989: Copy number analysis of Hodgkin lymphoma cell lines KM-H2 and L-428 Refer to individual Series *** This submission represents the microarray gene expression and microarray copy number components of the study
Project description:B-cell Non Hodgkin Lymphoma are a heterogenous group chracterized by a variety of genetic changes, including translocations, deletions and amplifications. Here we analyzed 10 B-NHL lines by Affymetrix SNP 6.0 to detect copy number changes. Specifically, we aim to identify cell lines suitable for testing the consequences of acute reintroduction of candidate tumor suppressor genes as they harbor deletions which include the candidate gene(s).
Project description:B-cell Non Hodgkin Lymphoma are a heterogenous group chracterized by a variety of genetic changes, including translocations, deletions and amplifications. Here we analyzed 10 B-NHL lines by Affymetrix SNP 6.0 to detect copy number changes. Specifically, we aim to identify cell lines suitable for testing the consequences of acute reintroduction of candidate tumor suppressor genes as they harbor deletions which include the candidate gene(s). 10 BNHL cell lines were grown in standard cell culture conditions. Genomic DNA was exptracted from frozen pellets and analyzed for copy number variations with Affymetrix SNP 6.0 Arrays
Project description:Illumina Infinium whole genome genotyping (WGG) arrays are increasingly being applied in cancer genomics to study gene copy number alterations and allele-specific aberrations such as loss-of-heterozygosity (LOH). Methods developed for normalization of WGG arrays have mostly focused on diploid, normal samples. However, for cancer samples genomic aberrations may confound normalization and data interpretation. Therefore, we examined the effects of the conventionally used normalization method for Illumina Infinium arrays when applied to cancer samples. We demonstrate an asymmetry in the detection of the two alleles for each SNP, which deleteriously influences both allelic proportions and copy number estimates. The asymmetry is caused by a remaining bias between the two dyes used in the Infinium II assay after using the normalization method in Illumina’s proprietary software (BeadStudio). We propose a quantile normalization strategy for correction of this dye bias. We tested the normalization strategy using 535 individual hybridizations from 10 data sets from the analysis of cancer genomes and normal blood samples generated on Illumina Infinium II 300k version 1 and 2, 370k and 550k BeadChips. We show that the proposed normalization strategy successfully removes asymmetry in estimates of both allelic proportions and copy numbers. Additionally, the normalization strategy reduces the technical variation for copy number estimates while retaining the response to copy number alterations. The proposed normalization strategy represents a valuable low-level analysis tool that improves the quality of data obtained from Illumina Infinium arrays, in particular when used for LOH and copy number variation studies.
Project description:Follicular lymphoma is the most common indolent non-Hodgkin's lymphoma involving germinal centre B cells, with a subset of patients undergoing transformation to a diffuse large B-cell lymphoma (DLBCL) morphology for which the clinical outcomes are poor. To elucidate the differences in copy number profiles between FL and tFL groups, we performed Affymetrix SNP 6.0 Array analysis on 31 paired FL-tFL cases. We wanted to identify and compare recurrent somatic copy number alterations (CNAs) between the two groups (FL vs. tFL). In addition, the concordance and discordance in the copy neutral loss of heterozygosity (cnLOH) between the two groups were also investigated to identify recurrent target gene regions. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from follicular lymphoma (FL), transformed follicular lymphoma (tFL) and matching germline (GL) sample (if available). Copy number analysis of Affymetrix SNP 6.0 Array were performed on 91 DNA samples, consisting of 31 patients. Among the 31 patients, 19 had matching germline samples, while 12 had no germline samples. The Log R Ratio (LRR) values and the B Allele Frequency (BAF) values were subsequently calculated to search for copy number aberrations and copy neutral (CN)-LOH in the FL and tFL samples. Paired and unpaired analyses were performed accordingly.
Project description:Follicular lymphoma (FL) is an indolent, but incurable subtype of non-Hodgkin lymphoma. These tumor harbor t (14;18) translocation in at least 90% of patients. Recently, activating EZH2 mutations have been Follicular lymphoma (FL) is an indolent, but incurable subtype of non-Hodgkin lymphoma. These tumor harbor t (14;18) translocation in at least 90% of patients. Recently, activating EZH2 mutations have been found in a significant number of patients with FL. Gene expression profiling (GEP) was performed to determine differential gene-expression between the EZH2 mutated vs unmutated subgroups in FL.
Project description:Follicular lymphoma is the most common indolent non-Hodgkin's lymphoma involving germinal centre B cells, with a subset of patients undergoing transformation to a diffuse large B-cell lymphoma (DLBCL) morphology for which the clinical outcomes are poor. To elucidate the differences in copy number profiles between FL and tFL groups, we performed Affymetrix SNP 6.0 Array analysis on 31 paired FL-tFL cases. We wanted to identify and compare recurrent somatic copy number alterations (CNAs) between the two groups (FL vs. tFL). In addition, the concordance and discordance in the copy neutral loss of heterozygosity (cnLOH) between the two groups were also investigated to identify recurrent target gene regions.
Project description:Follicular lymphoma (FL) constitutes the second most common non-Hodgkin lymphoma in the Western world. FL carries characteristic recurrent structural genomic aberrations. However, information regarding the coding genome in FL is still evolving. Here, we describe the results of massively parallel exome sequencing and high-resolution SNP 6.0 array profiling of 12 highly purified FL cases and validation of mutations in an expansion cohort of 45 cases. In addition to confirming high-frequency mutations in MLL2, CREBBP and BCL2, we report identification of 18 recurrently mutated genes in FL. These include novel mutations in MCL1, IRF8 and POU2FA/OCT2, and high-frequency mutations in various components of the linker histone HIST1H1. Further, multiple novel mutated genes located within regions of acquired uniparental disomy (aUPD) are identified, providing candidate genes for this common lesion type in FL. In aggregate, these data substantially broaden our understanding of the types and frequency of recurrently mutated genes and pathways in FL Twelve paired normal and tumor follicular lymphoma cases were profiled by SNP array for this study. However, in addition the data from 125 CEL files derived from the DNA of flow-sorted CD3+ cells from 125 CLL patients (122 CEL files from GSE30777) were used to firmly establish a normal copy number baseline for the dChip software to compute all subsequent normal and tumor DNA copy number values.
Project description:Renal tumors with complex morphology require extensive workup for accurate classification. Chromosomal aberrations that define subtypes of renal epithelial neoplasms have been reported. We explored if whole-genome chromosome copy number and loss-of-heterozygosity analysis with single nucleotide polymorphism (SNP) arrays can be used to identify these aberrations in cases where morphology was unable to definitively classify these tumors. Keywords: Chromosome copy number and LOH analysis (virtual karyotyping) with SNP Genotyping Arrays Keywords: Genome variation profiling by SNP array