ArticleOncotarget2016
Development of a novel HAC-based "gain of signal" quantitative assay for measuring chromosome instability (CIN) in cancer cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 31 citations in OpenAlex.
- Therapy enhancing chromosome instability may be advantageous forNAR cancer · 2025Article
- Review
- Centromeres in cancer: Unraveling the link between chromosomal instability and tumorigenesis.Medical oncology (Northwood, London, England) · 2024Review
- Kinesin-7 CENP-E in tumorigenesis: Chromosome instability, spindle assembly checkpoint, and applications.Frontiers in molecular biosciences · 2024Review
- Theranostic Interpolation of Genomic Instability in Breast Cancer.International journal of molecular sciences · 2022Review
- Novel assay to measure chromosome instability identifiesFrontiers in bioengineering and biotechnology · 2022Article
- Medium levels of transcription and replication related chromosomal instability are associated with poor clinical outcome.Scientific reports · 2021Article
- Targeting chromosome trisomy for chromosome editing.Scientific reports · 2021Article
- Human artificial chromosome (HAC) for measuring chromosome instability (CIN) and identification of genes required for proper chromosome transmission.Experimental cell research · 2020Review
- A novel assay to screen siRNA libraries identifies protein kinases required for chromosome transmission.Genome research · 2019Article
- GPR124 regulates microtubule assembly, mitotic progression, and glioblastoma cell proliferation.Glia · 2019Article
- Detecting Chromosome Instability in Cancer: Approaches to Resolve Cell-to-Cell Heterogeneity.Cancers · 2019Review
- Novel screen for anti-cancer drugs that elevate chromosome instability (CIN) using human artificial chromosome (HAC).Oncotarget · 2018Article
- Systematic Analysis of Compounds Specifically Targeting Telomeres and Telomerase for Clinical Implications in Cancer Therapy.Cancer research · 2018Article
- MAD2 Combined with Mitotic Spindle Apparatus (MSA) and Anticentromere Antibody (ACA) for Diagnosis of Small Cell Lung Cancer (SCLC).Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Human Artificial Chromosome with Regulated Centromere: A Tool for Genome and Cancer Studies.ACS synthetic biology · 2018Review
- Determinants and clinical implications of chromosomal instability in cancer.Nature reviews. Clinical oncology · 2018Review
- Method to Assemble Genomic DNA Fragments or Genes on Human Artificial Chromosome with Regulated Kinetochore Using a Multi-Integrase System.ACS synthetic biology · 2018Article
- Review
- Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 4 countries.
Funding
Abstract
Accumulating data indicates that chromosome instability (CIN) common to cancer cells can be used as a target for cancer therapy. At present the rate of chromosome mis-segregation is quantified by laborious techniques such as coupling clonal cell analysis with karyotyping or fluorescence in situ hybridization (FISH). Recently, a novel assay was developed based on the loss of a non-essential human artificial chromosome (HAC) carrying a constitutively expressed EGFP transgene ("loss of signal" assay). Using this system, anticancer drugs can be easily ranked on by their effect on HAC loss. However, it is problematic to covert this "loss of signal" assay into a high-throughput screen to identify drugs and mutations that increase CIN levels. To address this point, we re-designed the HAC-based assay. In this new system, the HAC carries a constitutively expressed shRNA against the EGFP transgene integrated into human genome. Thus, cells that inherit the HAC display no green fluorescence, while cells lacking the HAC do. We verified the accuracy of this "gain of signal" assay by measuring the level of CIN induced by known antimitotic drugs and added to the list of previously ranked CIN inducing compounds, two newly characterized inhibitors of the centromere-associated protein CENP-E, PF-2771 and GSK923295 that exhibit the highest effect on chromosome instability measured to date. The "gain of signal" assay was also sensitive enough to detect increase of CIN after siRNA depletion of known genes controlling mitotic progression through distinct mechanisms. Hence this assay can be utilized in future experiments to uncover novel human CIN genes, which will provide novel insight into the pathogenesis of cancer. Also described is the possible conversion of this new assay into a high-throughput screen using a fluorescence microplate reader to characterize chemical libraries and identify new conditions that modulate CIN level.
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Registered trials
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.