Cell models with inducible oncogenic translocations allow to evaluate the potential of drugs to favor secondary translocations

Шмакова, А. А.; Lomov, Nikolai; Viushkov, Vladimir S.; Tsfasman, Tatyana; Kozhevnikova, Yana; Sokolova, Darina V.; Pokrovsky, Vadim S.; Syrkina, M. S.; Germini, Diego; Rubtsov, Mikhail A.; Vassetzky, Yegor S.

doi:10.1002/cac2.12370

Cited by 6 publications

(7 citation statements)

References 10 publications

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“…Human cell lines (RPMI8866 and PRIESS) have been authenticated using STR profiling (Supporting Information: File , Supporting Information: Table ). We also created RPMI8866‐derived cell lines that inducibly expressed CRISPR/Cas9 and guide RNAs (gRNAs), targeting both MYC and IGH ; MYC only; IGH only or both AML and ETO loc as previously described 33 . These RMPI8866‐derived cell lines were named MYCIGHC9, MYCC9, IGHC9, and AMLETOC9, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…We also created RPMI8866-derived cell lines that inducibly expressed CRISPR/Cas9 and guide RNAs (gRNAs), targeting both MYC and IGH; MYC only; IGH only or both AML and ETO loc as previously described. 33 These RMPI8866-derived cell lines were named MYCIGHC9, MYCC9, IGHC9, and AMLETOC9, respectively. Cells were transfected and gRNAs efficiency was tested exploiting techniques and protocols developed in the laboratory.…”

Section: Cellsmentioning

confidence: 99%

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Epstein−Barr virus reactivation induces MYC‐IGH spatial proximity and t(8;14) in B cells

Sall

Шмакова

Karpukhina

et al. 2023

Journal of Medical Virology

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Burkitt lymphoma (BL) is a B cell malignancy associated with the Epstein−Barr virus (EBV). Most BL cases are characterized by a t(8;14) chromosomal translocation involving the MYC oncogene and the immunoglobulin heavy chain gene (IGH). The role of EBV in promoting this translocation remains largely unknown. Here we provide the experimental evidence that EBV reactivation from latency leads to an increase in the proximity between the MYC and IGH loci, otherwise located far away in the nuclear space both in B-lymphoblastoid cell lines and in patients' B-cells. Specific DNA damage within the MYC locus, followed by the MRE11-dependent DNA repair plays a role in this process. Using a CRISPR/Cas9-based B cell model to induce specific DNA double strand breaks in MYC and IGH loci, we have shown that the MYC-IGH proximity induced by EBV reactivation leads to an increased t(8;14) translocation frequency.

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Section: Methodsmentioning

confidence: 99%

Section: Cellsmentioning

confidence: 99%

Epstein−Barr virus reactivation induces MYC‐IGH spatial proximity and t(8;14) in B cells

Sall

Шмакова

Karpukhina

et al. 2023

Journal of Medical Virology

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“…Furthermore, an important clue comes from the fact that the expression lncRNAs is cell and tissue specific. It has long been questioned why different chromosomal aberrations occur in different cells 6 . It is plausible that lncRNAs, expressed in a particular cell type, might contribute to the appearance of cell‐specific chromosomal rearrangements between different loci via homologous regions.…”

Section: Figurementioning

confidence: 99%

“…It has long been questioned why different chromosomal aberrations occur in different cells. 6 It is plausible that lncRNAs, expressed in a particular cell type, might contribute to the appear-…”

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confidence: 99%

lncRNA: A new danger for genome integrity

Шмакова

Vassetzky

2023

Intl Journal of Cancer

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“…The advent of engineered nucleases provided a new opportunity to precisely study translocations by introducing DSBs in the regions of interest. Specific chromosomal translocations can now be generated from precisely induced DSBs using programmed nucleases such as zinc finger nucleases (ZFN), transcription activator-like effector nucleases (TALEN), and clustered regularly interspaced short palindromic repeats (CRISPR) [ 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 ]. A more sophisticated way to induce chromosomal translocations in cells would be to use proteins that naturally induce DNA damage and are known to be implicated in chromosomal translocations, reviewed in [ 85 , 86 ].…”

Section: Sources Of Dsbs In Vivo and Their Experimental Modeling For ...mentioning

confidence: 99%

Factors That Affect the Formation of Chromosomal Translocations in Cells

Canoy

Шмакова

Karpukhina

et al. 2022

Cancers

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Chromosomal translocations are products of the illegitimate repair of DNA double-strand breaks (DSBs). Their formation can bring about significant structural and molecular changes in the cell that can be physiologically and pathologically relevant. The induced changes may lead to serious and life-threatening diseases such as cancer. As a growing body of evidence suggests, the formation of chromosomal translocation is not only affected by the mere close spatial proximity of gene loci as potential translocation partners. Several factors may affect formation of chromosomal translocations, including chromatin motion to the potential sources of DSBs in the cell. While these can be apparently random events, certain chromosomal translocations appear to be cell-type-specific. In this review, we discuss how chromosomal translocations are formed and explore how different cellular factors contribute to their formation.

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Cell models with inducible oncogenic translocations allow to evaluate the potential of drugs to favor secondary translocations

Cited by 6 publications

References 10 publications

Epstein−Barr virus reactivation induces MYC‐IGH spatial proximity and t(8;14) in B cells

Epstein−Barr virus reactivation induces MYC‐IGH spatial proximity and t(8;14) in B cells

lncRNA: A new danger for genome integrity

Factors That Affect the Formation of Chromosomal Translocations in Cells

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