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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Nyckelord

CD5

cell lines

CLL

clonal evolution

subclones

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