A CRISPR/Cas9 Functional Screen Identifies Rare Tumor Suppressors

Area of Science:

• Oncology
• Genetics
• Cancer Research

Background:

• Vast tumor sequencing data presents challenges in identifying functional consequences of rare mutations.
• Distinguishing driver from passenger mutations is difficult, especially for rare variants.

Purpose of the Study:

• To uncover previously unsuspected rare oncogenic mutations in Burkitt's lymphoma.
• To validate the utility of in vivo CRISPR/Cas9 screens for identifying rare oncogenic modifiers.

Main Methods:

• Combined genome editing technology (CRISPR/Cas9) with a mouse cancer model.
• Conducted in vivo CRISPR/Cas9 screens to analyze tumor mutational data.

Main Results:

• Identified two candidate tumor suppressor genes.
• Demonstrated that the loss of these tumor suppressors cooperates with MYC over-expression to accelerate lymphomagenesis.

Conclusions:

• The study highlights the effectiveness of in vivo CRISPR/Cas9 screens in mouse models for discovering rare oncogenic mutations.
• This approach can identify and validate rare oncogenic modifier events within large tumor sequencing datasets.