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A genome-wide RNAi screen for novel CIN genes using human artificial chromosome
Mikhail Liskovykh1, Natalia Y Kochanova2, Chih-Yuan Chiang3
1Developmental Therapeutics Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
PNAS Nexus
|December 19, 2025
Summary
Researchers identified 44 key genes contributing to chromosome instability (CIN), a major cancer problem. Altered expression of these genes, particularly in mitotic regulators, correlates with poor patient survival and may offer new therapeutic targets.
Area of Science:
- Genetics
- Cancer Biology
- Molecular Oncology
Background:
- Chromosome instability (CIN) is a significant challenge in cancer research.
- Identifying genes that regulate CIN is crucial for understanding cancer progression and developing treatments.
Purpose of the Study:
- To conduct a genome-wide RNAi screen to identify genes contributing to CIN.
- To find novel genes and pathways involved in maintaining chromosomal stability.
Main Methods:
- A genome-wide RNAi screen using a human artificial chromosome in a sensitized system.
- Screened 18,658 genes to measure CIN.
- Secondary screen identified 44 top CIN-associated genes.
- Guilt-by-association analysis with cancer cell line proteomic data.
Main Results:
- Identified 834 candidate CIN genes, with 44 showing pronounced phenotypes.
- The 44 genes strongly correlated with mitotic regulators.
- Altered expression of these genes is linked to poor prognosis in multiple cancer types.
- Specific gene downregulation (AMY2B, ALAD, PDGFRA, PPIE, VEZ1, TTC19) associated with poor survival in lung, adrenocortical, ovarian, and breast cancers.
Conclusions:
- The identified genes serve as potential prognostic markers for cancer patient survival.
- These genes may represent novel therapeutic targets for mitigating CIN and treating cancer.
