2.50
Hdl Handle:
http://hdl.handle.net/10033/620137
Title:
Subclones in B-lymphoma cell lines: isogenic models for the study of gene regulation.
Authors:
Quentmeier, Hilmar; Pommerenke, Claudia ( 0000-0002-9448-416X ) ; Ammerpohl, Ole; Geffers, Robert ( 0000-0003-4409-016X ) ; Hauer, Vivien; MacLeod, Roderick Af; Nagel, Stefan; Romani, Julia; Rosati, Emanuela; Rosén, Anders; Uphoff, Cord C; Zaborski, Margarete; Drexler, Hans G
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.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig.
Citation:
Subclones in B-lymphoma cell lines: isogenic models for the study of gene regulation. 2016: Oncotarget
Journal:
Oncotarget
Issue Date:
23-Aug-2016
URI:
http://hdl.handle.net/10033/620137
DOI:
10.18632/oncotarget.11524
PubMed ID:
27566572
Type:
Article
ISSN:
1949-2553
Appears in Collections:
publications of the research group genomeanalytics (GMAK)

Full metadata record

DC FieldValue Language
dc.contributor.authorQuentmeier, Hilmaren
dc.contributor.authorPommerenke, Claudiaen
dc.contributor.authorAmmerpohl, Oleen
dc.contributor.authorGeffers, Roberten
dc.contributor.authorHauer, Vivienen
dc.contributor.authorMacLeod, Roderick Afen
dc.contributor.authorNagel, Stefanen
dc.contributor.authorRomani, Juliaen
dc.contributor.authorRosati, Emanuelaen
dc.contributor.authorRosén, Andersen
dc.contributor.authorUphoff, Cord Cen
dc.contributor.authorZaborski, Margareteen
dc.contributor.authorDrexler, Hans Gen
dc.date.accessioned2016-09-14T13:01:59Z-
dc.date.available2016-09-14T13:01:59Z-
dc.date.issued2016-08-23-
dc.identifier.citationSubclones in B-lymphoma cell lines: isogenic models for the study of gene regulation. 2016: Oncotargeten
dc.identifier.issn1949-2553-
dc.identifier.pmid27566572-
dc.identifier.doi10.18632/oncotarget.11524-
dc.identifier.urihttp://hdl.handle.net/10033/620137-
dc.description.abstractGenetic 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.en
dc.languageENG-
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleSubclones in B-lymphoma cell lines: isogenic models for the study of gene regulation.-
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig.en
dc.identifier.journalOncotargeten

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