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Series GSE56311 Query DataSets for GSE56311
Status Public on Mar 02, 2015
Title Integrative profiling of follicular lymphoma at diagnosis and relapse
Organism Homo sapiens
Experiment type Genome variation profiling by SNP array
Expression profiling by array
Summary Follicular lymphoma (FL) is incurable with conventional therapies and has a clinical course typified by multiple relapses after therapy. These tumors are genetically characterized by B-cell leukemia/lymphoma 2 (BCL2) translocation and mutation of genes involved in chromatin modification. By analyzing purified tumor cells, we identified additional novel recurrently mutated genes and confirmed mutations of one or more chromatin modifier genes within 96% of FL tumors and two or more in 76% of tumors. We defined the hierarchy of somatic mutations arising during tumor evolution by analyzing the phylogenetic relationship of somatic mutations across the coding genomes of 59 sequentially acquired biopsies from 22 patients. Among all somatically mutated genes, CREBBP mutations were most significantly enriched within the earliest inferable progenitor. These mutations were associated with a signature of decreased antigen presentation characterized by reduced transcript and protein abundance of MHC class II on tumor B cells, in line with the role of CREBBP in promoting class II transactivator (CIITA)-dependent transcriptional activation of these genes. CREBBP mutant B cells stimulated less proliferation of T cells in vitro compared with wild-type B cells from the same tumor. Transcriptional signatures of tumor-infiltrating T cells were indicative of reduced proliferation, and this corresponded to decreased frequencies of tumor-infiltrating CD4 helper T cells and CD8 memory cytotoxic T cells. These observations therefore implicate CREBBP mutation as an early event in FL evolution that contributes to immune evasion via decreased antigen presentation.
 
Overall design [copy number] B-cells were purified from cyropreserved tumor cell suspensions by FACS, DNA isolated, and interogated using Affymetrix 250K Nsp SNP microarrays.
Aim: To track the evolution of genetic alterations during progression of follicular lymphoma.
One array per tumor.

[gene expression] Gene expression profiling of purified B and T cells from follicular lymphoma tumors at diagnosis and relapse
Tumor B-cells (CD19+CD20+CD10+) and tumor-infiltrating T-cells (CD5+CD19-) were sorted from cryopreserved follicular lymphoma biopsies by fluorescence activated cell sorting. DNA and RNA were isolated using Qiagen AllPrep kits, and RNA was interrogated using Affymetrix U133plus2 gene expression microarray.
 
Contributor(s) Green MR, Alizadeh AA
Citation(s) 25713363
Submission date Mar 27, 2014
Last update date Mar 25, 2019
Contact name Michael R Green
E-mail(s) mgreen5@mdanderson.org
Organization name MD Anderson Cancer Center
Department Lymphoma/Myeloma
Street address 1515 Holcombe Blvd, Unit 903
City Houston
State/province TX
ZIP/Postal code 77030
Country USA
 
Platforms (2)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
GPL3718 [Mapping250K_Nsp] Affymetrix Mapping 250K Nsp SNP Array
Samples (123)
GSM1358857 LPJ040_Diagnosis_Site1
GSM1358858 LPJ040_Diagnosis_Site2
GSM1358859 LPJ040_Relapse1
Relations
BioProject PRJNA242890

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE56311_RAW.tar 2.8 Gb (http)(custom) TAR (of CEL, CNCHP)
Processed data included within Sample table
Processed data provided as supplementary file

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