Related Experiment Video

Updated: Oct 10, 2025

HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries
10:10

HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries

Published on: March 31, 2019

8.5K

Uncovering Tumorigenesis Circuitry with Combinatorial CRISPR

Samson H Fong1,2, Brenton P Munson1,2, Trey Ideker3,2,4,5

  • 1Division of Genetics, Department of Medicine, University of California San Diego, La Jolla, California.

Cancer Research
|December 16, 2021
PubMed

Insights

Scientists mapped gene interactions driving cancer by knocking out gene pairs. They found NF2, PTEN, and TP53 collaborate to promote tumor growth, revealing complex oncogenesis networks.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Cancer development involves alterations in multiple driver genes, but the specific combinations promoting oncogenesis remain unclear.
  • Understanding gene interactions is crucial for deciphering complex cancer networks and developing targeted therapies.

Purpose of the Study:

  • To systematically identify synergistic interactions among tumor suppressor genes using a high-throughput CRISPR-Cas9 screening approach.
  • To map the complex genetic networks that collaborate to drive tumorigenesis.

Main Methods:

  • Utilized CRISPR-Cas9 gene editing to perform pairwise knockouts of 52 tumor suppressor genes across various cancer models.
  • Conducted interaction screens in both cell cultures and mouse models to identify cooperating gene alterations.
  • Employed single-cell transcriptomic profiling to characterize synergistic gene interactions in detail.

Main Results:

  • Identified significant cooperation among NF2, PTEN, and TP53 genes in promoting cell growth across multiple tumorigenesis models.
  • Revealed other strongly synergistic interactions between tumor suppressor genes.
  • Demonstrated the scalability of the CRISPR-based screening approach for mapping gene networks.

Conclusions:

  • The study presents a scalable methodology to move beyond single-gene drivers and map complex gene networks in cancer.
  • The findings highlight the collaborative roles of specific tumor suppressor genes, such as NF2, PTEN, and TP53, in oncogenesis.
  • This approach provides a foundation for understanding combinatorial gene alterations in cancer development.

More Related Videos

Mosaic Zebrafish Transgenesis for Functional Genomic Analysis of Candidate Cooperative Genes in Tumor Pathogenesis09:45

Mosaic Zebrafish Transgenesis for Functional Genomic Analysis of Candidate Cooperative Genes in Tumor Pathogenesis

Published on: March 31, 2015

11.4K
Genome-Wide CRISPR Screen for Unveiling Radiosensitive and Radioresistant Genes08:32

Genome-Wide CRISPR Screen for Unveiling Radiosensitive and Radioresistant Genes

Published on: May 23, 2025

608

Related Concept Videos

CRISPR and crRNAs02:53

CRISPR and crRNAs

Bacteria and archaea are susceptible to viral infections just like eukaryotes; therefore, they have developed a unique adaptive immune system to protect themselves. Clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins (CRISPR-Cas) are present in more than 45% of known bacteria and 90% of known archaea.
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...
17.8K
Conservative Site-specific Recombination and Phase Variation02:53

Conservative Site-specific Recombination and Phase Variation

Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
6.2K
Homologous Recombination02:31

Homologous Recombination

The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
55.2K
Combinatorial Gene Control02:33

Combinatorial Gene Control

Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
8.6K