Oncotarget

Research Papers:

Subclones in B-lymphoma cell lines: isogenic models for the study of gene regulation

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 and Hans G Drexler

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Oncotarget. 2016; 7:63456-63465. https://doi.org/10.18632/oncotarget.11524

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Abstract

Hilmar Quentmeier1, Claudia Pommerenke1, Ole Ammerpohl2, Robert Geffers3, Vivien Hauer1, Roderick AF MacLeod1, Stefan Nagel1, Julia Romani1, Emanuela Rosati4, Anders Rosén5, Cord C Uphoff1, Margarete Zaborski1, Hans G Drexler1

1Leibniz-Institute DSMZ-German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany

2Institute of Human Genetics, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Kiel, Germany

3Genome Analytics Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany

4Department of Experimental Medicine, Bioscience and Medical Embryology Section, University of Perugia, Perugia, Italy

5Department of Clinical and Experimental Medicine, Division of Cell Biology, Linköping University, Linköping, Sweden

Correspondence to:

Hilmar Quentmeier, email: [email protected]

Keywords: CD5, cell lines, CLL, clonal evolution, subclones

Received: June 07, 2016     Accepted: August 15, 2016     Published: August 23, 2016

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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