Comparative High-Resolution Transcriptome Sequencing of Lymphoma Cell Lines and de novo Lymphomas Reveals Cell-Line-Specific Pathway Dysregulation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA447614 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6912700.fastq.gz | Fastqsanger.gz | |||
| SRR6912700_1.fastq.gz | Fastqsanger.gz | |||
| SRR6912700_2.fastq.gz | Fastqsanger.gz | |||
| SRR6912710_1.fastq.gz | Fastqsanger.gz | |||
| SRR6912710_2.fastq.gz | Fastqsanger.gz |
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Project description:In dogs as well as humans, lymphoma is one of the most common hematopoietic malignancies. Furthermore, due to its characteristics, canine lymphoma is recognized as a clinically relevant in vivo model to study the corresponding human disease. Immortalized cell lines are widely used as in vitro models to evaluate novel therapeutic agents and characterize their molecular mechanisms. However, it is known that long-term cultivation leads to clonal selection, genetic instability, and loss of the initial heterogenic character, limiting the usefulness of cell lines as preclinical models. Herein, we present a systematic characterization and comparison of the transcriptomic landscape of canine primary B- and T-cell lymphomas, five lymphoid cell lines (CLBL-1, CLBL-1M, GL-1, CL-1, and OSW) and four non-neoplastic control samples. We found that lymphomas and cell lines exhibit a common "differentiation and proliferation signature". However, our analysis also showed that, independently of the cell of origin, the transcriptional signatures of lymphomas are more similar to each other than they are to those of cell lines. In particular, we observed that not all common therapeutic targets are similarly expressed between lymphomas and lymphoid cell lines, and provide evidence that different lymphoid cell-lines should be used to model distinct aspects of lymphoma dysregulation.
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Project description:MYC translocations are the biologic hallmark of Burkitt lymphomas but also occur in other mature B-cell lymphomas. If accompanied by chromosomal breaks targeting the BCL2 and/or BCL6 oncogenes, these MYC translocation-positive (MYC+) lymphomas are called double-hit lymphomas (DHLs); otherwise, the term single-hit lymphoma (SHL) is applied. In order to characterize the biologic features of these MYC+ lymphomas other than Burkitt lymphomas, we explored, after exclusion of molecular Burkitt lymphoma (mBL) as defined by gene expression profiling (GEP), the molecular, pathological and clinical aspects of 80 MYC translocation (MYC+) lymphomas (31 SHL, 26 BCL2+/MYC+, 14 BCL6+/MYC+, 6 BCL2+/BCL6+/MYC+ and 3 MYC+ lymphomas with unknown BCL6 status). Comparison of SHL and DHL revealed no difference in frequency of MYC partner (IG/non-IG), genomic complexity or MYC expression and no differences in GEP. DHL showed a more frequent GCB-like GEP and higher IGH and MYC mutation rates. GEP revealed 130 differentially expressed genes between BCL6+/MYC+ and BCL2+/MYC+ DHL. BCL2+/MYC+ DHL showed a more frequent GCB-like GEP. Analysis of all lymphomas according to MYC partner (IG/non-IG) revealed no substantial differences. In contrast to mBL and lymphomas without MYC break, SHL and DHL patients had similar poor outcome. Our data suggest that after excluding mBL, MYC+ lymphomas could be biologically widely lumped without further need for subclassification. 32 diffuse large B-cell lymphoma samples were hybridized to HG-U133A Affymetrix GeneChips. In addition, this study contains 30 already published samples, which contribute to GSE4475 (Hummel et al. 2006 (PMID 16760442)), as well as 18 already published samples from GSE22470 (Salaverria et al. 2011 (PMID 21487109)). No re-normalisation of the published samples was performed. The complete dataset representing: (1) the 32 diffuse large B-cell lymphoma Samples, (2) the 30 Samples from GSE4475 and (3) the 18 Samples from GSE22470, is linked below as a supplementary file
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