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Subclones in B-lymphoma cell lines: isogenic models for the studyof gene regulation
Leibniz-Institute DSMZ-German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany.
Leibniz-Institute DSMZ-German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany.
Institute of Human Genetics, Christian-Albrechts- University Kiel and University Hospital Schleswig-Holstein, Kiel, Germany.
Genome Analytics Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany.
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2016 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553Article in journal (Refereed) Accepted
Abstract [en]

Genetic heterogeneity though common in tumors has been rarely documented in celllines. To examine how often B-lymphoma cell lines are comprised of subclones, weperformed immunoglobulin (IG) heavy chain hypermutation analysis. Revealing thatsubclones 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 alsoidentified in 2/284 leukemia/lymphoma cell lines exhibiting bimodal CD markerexpression. We successfully isolated 10 subclones from four cell lines (HG3, SUDHL-5, TMD-8, U-2932). Whole exome sequencing was performed to molecularlycharacterize these subclones. We describe in detail the clonal structure of cell lineHG3, derived from chronic lymphocytic leukemia. HG3 consists of three subcloneseach bearing clone-specific aberrations, gene expression and DNA methylationpatterns. While donor patient leukemic cells were CD5+, two of three HG3 subcloneshad independently lost this marker. CD5 on HG3 cells was regulated byepigenetic/transcriptional mechanisms rather than by alternative splicing as reportedhitherto. In conclusion, we show that the presence of subclones in cell lines carryingindividual mutations and characterized by sets of differentially expressed genes is notuncommon. We show also that these subclones can be useful isogenic models forregulatory and functional studies.

Place, publisher, year, edition, pages
Impact Journals, LLC , 2016.
Keyword [en]
CD5, cell lines, CLL, clonal evolution, subclones
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-130591OAI: oai:DiVA.org:liu-130591DiVA: diva2:953356
Available from: 2016-08-17 Created: 2016-08-17 Last updated: 2016-08-24

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Rosén, Anders
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Division of Cell BiologyFaculty of Medicine and Health Sciences
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