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Modeling sarcoma relevant translocations using CRISPR-Cas9 in human embryonic stem derived mesenchymal precursors
Fabio Vanoli1, Cristina R Antonescu1
1Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Abstract:
The role of cancer relevant translocations in tumorigenesis has been historically hampered by the lack of faithful in vitro and in vivo models. The development of the latest genome editing tools (e.g., CRISPR-Cas9) allowed modeling of various chromosomal translocations with different effects on proliferation and transformation capacity depending on the cell line used and secondary genetic alterations. The cellular context is particularly relevant in the case of oncogenic fusions expressed in sarcomas whose histogenesis remain uncertain. Moreover, recent studies have emphasized the increased frequency of gene fusion promiscuity across different mesenchymal tumor entities, which are clinicopathologically unrelated. This review provides a summary of different strategies utilized to generate cancer models with a focus on fusion-driven mesenchymal neoplasia.
Insights
Creating accurate cancer models for studying translocations is challenging. Genome editing tools like CRISPR-Cas9 enable better in vitro and in vivo models for fusion-driven cancers, particularly sarcomas.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Cancer translocations are crucial in tumorigenesis but modeling them has been difficult.
- Existing models often lack fidelity, hindering the study of translocation-driven cancer development.
- The cellular context significantly influences the impact of oncogenic fusions, especially in sarcomas.
Purpose of the Study:
- To review strategies for generating cancer models, focusing on fusion-driven mesenchymal neoplasia.
- To highlight the role of genome editing tools in creating accurate translocation models.
- To discuss the implications of gene fusion promiscuity in mesenchymal tumors.
Main Methods:
- Review of scientific literature on cancer modeling techniques.
- Focus on genome editing tools such as CRISPR-Cas9.
- Analysis of studies modeling chromosomal translocations and gene fusions.
Main Results:
- Genome editing tools facilitate the creation of diverse chromosomal translocation models.
- These models reveal varied effects on proliferation and transformation based on cellular context.
- Evidence suggests increased gene fusion promiscuity across unrelated mesenchymal tumor types.
Conclusions:
- Advanced genome editing tools improve the fidelity of cancer models for translocation research.
- Understanding cellular context is vital for interpreting oncogenic fusion effects in sarcomas.
- Fusion promiscuity underscores the need for robust models in studying mesenchymal neoplasia.
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