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Mutations of multiple genes deregulate the NF-kB pathway in diffuse large B cell lymphoma

GSE12195 Homo sapiens (human) Expression microarray 136 samples Submitted 2009/04/10 Platform GPL570
At a glance

Expression microarray · human · 136 samples

What it is
Expression microarrayGene activity read on a chip (the older technology that RNA-seq replaced).
Organism
Homo sapiens (human)
Samples
136 samples: 9 conditions, mostly with about 5 replicates eachGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed expression table (series matrix) and the array files, from NCBI.
Summary (written by the submitters)
Diffuse large B-cell lymphoma (DLBCL), the most common form of lymphoma in adulthood, comprises multiple biologically and clinically distinct subtypes including germinal center B cell-like (GCB) and activated B cell like (ABC) DLBCL. Gene expression profile studies have shown that its most aggressive subtype, ABC-DLBCL, is associated with constitutive activation of the NF-kB transcription complex.
Read the full summary ↓
However, except for a small fraction of cases, it remains unclear whether NF-kB activation in these tumors represents an intrinsic program of the tumor cell of origin or a pathogenetic event. Here we show that >50% of ABC-DLBCL and a smaller fraction of GCB-DLBCL carry somatic mutations at multiple genes, including negative (TNFAIP3/A20) and positive (CARD11, TRAF2, TRAF5, MAP3K7/TAK1 and TNFRSF11A/RANK) regulators of NF-kB. Of these, the A20 gene, which encodes for a ubiquitin-modifying enzyme involved in termination of NF-kB responses, is the most commonly affected one, with ~30% of the patients displaying biallelic inactivation by mutations and/or deletions, suggesting a tumor suppressor role. Less frequently, missense mutations of TRAF2 and CARD11 produce molecules with significantly enhanced ability to activate NF-kB. Thus, our results demonstrate that NF-kB activation in DLBCL is caused by genetic lesions affecting multiple genes, whose loss or activation may promote lymphomagenesis by leading to abnormally prolonged NF-kB responses. We show that most ABC-DLBCL and a smaller fraction of GCB-DLBCL display genetic lesions affecting multiple NFkB pathway genes, with A20 representing the most frequently mutated gene Keywords: Phenotypic characterization of human DLBCL.
This dataset
Download · which file do I need?

Direct links to NCBI, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need.

All supplementary files ↗
3 · The original raw files

Whole study · RAW.tar

Everything the authors deposited as one archive (GSE12195_RAW.tar), including the raw array or instrument files. Can be large; the picker in step 2 takes just the samples you need.

What the files usually look like: For arrays the series matrix is normally the normalised expression table you want; the raw array files (CEL and similar) are in the RAW.tar.

Also filed as BioProject PRJNA113415. Searching any of these in the dataset finder brings you back here.

Study design
9 conditions, mostly with about 5 replicates each
DLBCL biopsy, sample ×72 Follicular lymphoma_FL.E ×29 Follicular lymphoma_FLB ×8 Germinal Center Centroblasts, sample ×5 Germinal Center Centrocytes, sample ×5 Naïve B cells_N1 4 ×3 Memory B cells_M4 ×3 Naïve B cells_N ×2 +8 more

Supports a between-group comparison across 129 samples.

How we read this: 9 replicated groups read from 136 sample titles; they account for 129 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

+ 96 more — browse all 136 samples with per-sample file links →

Datasets on a similar topic

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