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Updated: Jul 24, 2025

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Oncogene-like addiction to aneuploidy in human cancers

Vishruth Girish1,2, Asad A Lakhani3, Sarah L Thompson1

  • 1Yale University School of Medicine, New Haven, CT 06511, USA.

Science (New York, N.Y.)
|July 6, 2023
PubMed

Insights

Most cancers have aneuploidy, an abnormal chromosome number. Researchers developed ReDACT (Restoring Disomy in Aneuploid cells using CRISPR Targeting) tools to remove aneuploidies, finding chromosome 1q trisomy drives cancer growth by suppressing p53 signaling.

Area of Science:

  • Cancer Biology
  • Genetics
  • Chromosomal Abnormalities

Background:

  • Aneuploidy, an abnormal chromosome number, is common in cancers but its role in tumor development is debated.
  • Understanding the functional impact of specific aneuploidies is crucial for cancer research.

Purpose of the Study:

  • To investigate the functional significance of specific aneuploidies in cancer development.
  • To develop tools for precise manipulation of aneuploidy in cancer cells.

Main Methods:

  • Development of ReDACT (Restoring Disomy in Aneuploid cells using CRISPR Targeting) tools for chromosome engineering.
  • Creation of isogenic cancer cell lines with and without specific aneuploidies.
  • Analysis of gene expression and signaling pathways, including p53 and MDM4.

Main Results:

  • Trisomy of chromosome 1q was identified as essential for malignant growth in cancers with this alteration.
  • Chromosome 1q gain upregulates MDM4 expression, leading to p53 pathway suppression.
  • TP53 mutations and 1q aneuploidy are mutually exclusive in human cancers.

Conclusions:

  • Tumor cells can exhibit dependence on specific aneuploidies, termed 'aneuploidy addictions'.
  • Targeting these aneuploidy addictions presents a potential therapeutic strategy for cancer treatment.

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