Title |
Subclones in B-lymphoma cell lines: isogenic models for the study of gene regulation
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Published in |
Oncotarget, August 2016
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DOI | 10.18632/oncotarget.11524 |
Pubmed ID | |
Authors |
Hilmar Quentmeier, Claudia Pommerenke, Ole Ammerpohl, Robert Geffers, Vivien Hauer, Roderick AF MacLeod, Stefan Nagel, Julia Romani, Emanuela Rosati, Anders Rosén, Cord C Uphoff, Margarete Zaborski, Hans G Drexler |
Abstract |
Genetic heterogeneity though common in tumors has been rarely documented in cell lines. To examine how often B-lymphoma cell lines are comprised of subclones, we performed immunoglobulin (IG) heavy chain hypermutation analysis. Revealing that subclones are not rare in B-cell lymphoma cell lines, 6/49 IG hypermutated cell lines (12%) consisted of subclones with individual IG mutations. Subclones were also identified in 2/284 leukemia/lymphoma cell lines exhibiting bimodal CD marker expression. We successfully isolated 10 subclones from four cell lines (HG3, SU-DHL-5, TMD-8, U-2932). Whole exome sequencing was performed to molecularly characterize these subclones. We describe in detail the clonal structure of cell line HG3, derived from chronic lymphocytic leukemia. HG3 consists of three subclones each bearing clone-specific aberrations, gene expression and DNA methylation patterns. While donor patient leukemic cells were CD5+, two of three HG3 subclones had independently lost this marker. CD5 on HG3 cells was regulated by epigenetic/transcriptional mechanisms rather than by alternative splicing as reported hitherto. In conclusion, we show that the presence of subclones in cell lines carrying individual mutations and characterized by sets of differentially expressed genes is not uncommon. We show also that these subclones can be useful isogenic models for regulatory and functional studies. |
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Geographical breakdown
Country | Count | As % |
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Unknown | 4 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 4 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 25 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 6 | 24% |
Student > Doctoral Student | 3 | 12% |
Student > Master | 3 | 12% |
Researcher | 3 | 12% |
Student > Bachelor | 2 | 8% |
Other | 3 | 12% |
Unknown | 5 | 20% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 9 | 36% |
Medicine and Dentistry | 4 | 16% |
Agricultural and Biological Sciences | 3 | 12% |
Immunology and Microbiology | 1 | 4% |
Unspecified | 1 | 4% |
Other | 2 | 8% |
Unknown | 5 | 20% |