E-MTAB-4956 - human SU-DHL-5 and TMD-8 B-lymphome cell line subclones
Released on 30 September 2016, last updated on 8 November 2016
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 in detail describe the clonal structure of cell line HG3, derived from chronic lymphocytic leukemia. HG3 consists of three lineages 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.
DNA-seq, genotype design, strain or line design
Subclones in B-lymphoma cell lines: isogenic models for the study of gene regulation. Quentmeier H, Pommerenke C, Ammerpohl O, Geffers R, Hauer V, MacLeod RA, Nagel S, Romani J, Rosati E, Rosén A, Uphoff CC, Zaborski M, Drexler HG. (2016), PMID:27566572