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Related Concept Videos

Genetic Screens02:46

Genetic Screens

5.9K
Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing  genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which...
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Cancer-Critical Genes I: Proto-oncogenes01:33

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Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
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Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

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Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
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Cancer-Critical Genes II: Tumor Suppressor Genes01:05

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CRISPR01:59

CRISPR

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Genome editing technologies allow scientists to modify an organism’s DNA via the addition, removal, or rearrangement of genetic material at specific genomic locations. These types of techniques could potentially be used to cure genetic disorders such as hemophilia and sickle cell anemia. One popular and widely used DNA-editing research tool that could lead to safe and effective cures for genetic disorders is the CRISPR-Cas9 system. CRISPR-Cas9 stands for Clustered Regularly Interspaced...
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CRISPR Screening in Hepatocellular Carcinoma: From Tumor Progression to Immune Evasion and Therapeutic Resistance.

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Genome-Wide CRISPR Screening Identifies Genetic Modulators of Amyloid Precursor Protein Processing.

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CRISPR Applications in Alzheimer's Disease: From High-Throughput Genetic Screening to Precision Editing and CNS Delivery.

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Updated: Apr 15, 2026

Genome-Wide CRISPR Screen for Unveiling Radiosensitive and Radioresistant Genes
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Functional CRISPR Screens Define Genetic Drivers for Cancer Transformation and Progression from Non-Cancerous Cells.

Shixin Ma1,2,3,4, You Li1,2,3,4, Teng Fei1,2,3,4

  • 1Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China.

International Journal of Molecular Sciences
|April 14, 2026
PubMed
Summary

Identifying early cancer drivers is key. This study found TP53 and NF1 consistently initiate tumors and metastasis across contexts, unlike most context-specific genetic alterations.

Keywords:
CRISPR screenbreast cancerfibroblastimmortalizationliver cancermetastasistransformation

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Area of Science:

  • Oncology
  • Genetics
  • Cancer Biology

Background:

  • Tumor initiation and metastasis are driven by genetic alterations affecting critical cellular pathways.
  • The specific genetic drivers and their context-dependent roles in early cancer development remain largely unknown.

Purpose of the Study:

  • To systematically identify and characterize the initial genetic drivers of malignant transformation across diverse cancer types, species, and microenvironments.
  • To understand the context dependency of these drivers and their convergence on core cellular pathways.

Main Methods:

  • Customized clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) knockout libraries were created targeting genes frequently mutated or downregulated in liver hepatocellular carcinoma (LIHC) and breast carcinoma (BRCA).
  • Functional screens were performed in non-cancerous mouse and human fibroblast cell lines under 2D, 3D, and in vivo conditions to identify genes promoting immortalization, tumorigenesis, and metastasis.

Main Results:

  • TP53 and NF1 were identified as pan-context drivers, consistently promoting cancer progression across different settings for both LIHC and BRCA.
  • Most other identified drivers exhibited species-, tissue-, and microenvironment-specific effects with limited overlap between models.
  • All identified drivers converged on key pathways, including epigenetic regulation, metabolic reprogramming, and growth factor signaling.

Conclusions:

  • This study defines critical genetic barriers to malignant transformation in normal cells, providing novel insights into early cancer evolution.
  • TP53 and NF1 represent fundamental drivers of cancer initiation and metastasis, irrespective of cellular context.
  • The findings offer a new framework for understanding early cancer development and identifying potential therapeutic targets.