Evidence map›Paper›PMID 41416224›Full record

ArticlePNAS nexus2025

A genome-wide RNAi screen for novel CIN genes using human artificial chromosome.

Mikhail Liskovykh, Natalia Y Kochanova, Chih-Yuan Chiang, Anjali Dhall, Vasilisa Aksenova, Yu-Chi Chen, William C Reinhold, Mary Dasso, Anish Thomas, Ken Chih-Chien Cheng and 4 more

Abstract read
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Article in PNAS nexus, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

14 authors.

Mikhail LiskovykhDevelopmental Therapeutics Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.ORCID https://orcid.org/0000-0002-6760-8331
Natalia Y KochanovaWellcome Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3BF, United Kingdom.ORCID https://orcid.org/0000-0001-9951-8333
Chih-Yuan ChiangFunctional Genomics Laboratory, National Center for Advancing Translational Sciences, NIH, Rockville, MD 20850, USA.
Anjali DhallDevelopmental Therapeutics Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Vasilisa AksenovaDivision of Molecular and Cellular Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.ORCID https://orcid.org/0000-0001-7325-3453
Yu-Chi ChenFunctional Genomics Laboratory, National Center for Advancing Translational Sciences, NIH, Rockville, MD 20850, USA.
William C ReinholdDevelopmental Therapeutics Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.ORCID https://orcid.org/0000-0001-5513-9323
Mary DassoDivision of Molecular and Cellular Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.ORCID https://orcid.org/0000-0002-5410-1371
Anish ThomasDevelopmental Therapeutics Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.ORCID https://orcid.org/0000-0003-3293-3115
Ken Chih-Chien ChengFunctional Genomics Laboratory, National Center for Advancing Translational Sciences, NIH, Rockville, MD 20850, USA.
Yves PommierDevelopmental Therapeutics Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
William C EarnshawWellcome Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3BF, United Kingdom.ORCID https://orcid.org/0000-0002-7191-0621
Vladimir LarionovDevelopmental Therapeutics Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.ORCID https://orcid.org/0000-0002-7996-4894
Natalay KouprinaDevelopmental Therapeutics Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.ORCID https://orcid.org/0000-0001-8690-5625

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chromosome instability (CIN) remains among the most important problems in modern cancer research. In this study, we conducted a genome-wide RNAi screen to identify genes that contribute to CIN. To achieve this, we used a human artificial chromosome in a novel sensitized screen to measure CIN. We screened 18,658 genes for their roles in maintaining chromosomal stability and identified 834 candidates as potential CIN genes. A secondary RNAi screen identified 44 genes with the most pronounced CIN phenotypes. In guilt-by-association analysis using a published set of 8,498 proteins across a panel of 949 cancer cell lines, this cohort of 44 genes displayed a striking correlation with mitotic regulators. Furthermore, altered expression of these proteins was associated with a poor prognosis across multiple cancer types. Specifically, downregulation of AMY2B, ALAD, PDGFRA, PPIE, VEZ1, and TTC19 is associated with poor survival in two or more of the following: small cell lung cancer, lung adenocarcinoma, adrenocortical carcinoma, ovarian cancer, and breast cancer. The genes identified in this screen hold potential as prognostic markers for patient survival across several cancer types and could potentially serve as targets for the development of new therapeutic approaches aimed at mitigating CIN.

Indexed as

chromosome instabilityhuman artificial chromosomesmitosis

Identifiers

PMID41416224
PMCPMC12709509

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.