ArticleBMC cancer2013
A new assay for measuring chromosome instability (CIN) and identification of drugs that elevate CIN in cancer cells.
Article in BMC cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 46 citations in OpenAlex.
- HSP90 inhibition disrupts telomere maintenance and promotes chromosomal instability (CIN) in cancer cells.Research square · 2026Article
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- The homologous recombination factors BRCA2 and PALB2 interplay with mismatch repair pathways to maintain centromere stability and cell viability.Cell reports · 2025Article
- TRACERx analysis identifies a role for FAT1 in regulating chromosomal instability and whole-genome doubling via Hippo signalling.Nature cell biology · 2025Article
- Review
- The reckoning of chromosomal instability: past, present, future.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2024Review
- Chromosomal instability and inflammation: a catch-22 for cancer cells.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2023Review
- Novel assay to measure chromosome instability identifiesFrontiers in bioengineering and biotechnology · 2022Article
- Terpyridine platinum compounds induce telomere dysfunction and chromosome instability in cancer cells.Oncotarget · 2021Article
- Population and subspecies diversity at mouse centromere satellites.BMC genomics · 2021Article
- Disruption of the MSL complex inhibits tumour maintenance by exacerbating chromosomal instability.Nature cell biology · 2021Article
- Centrosome amplification is a frequent event in circulating tumor cells from subjects with metastatic breast cancer.Molecular oncology · 2020Article
- Chromosomal instability in untreated primary prostate cancer as an indicator of metastatic potential.BMC cancer · 2020Article
- 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
- 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
- Human Artificial Chromosome with Regulated Centromere: A Tool for Genome and Cancer Studies.ACS synthetic biology · 2018Review
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundAneuploidy is a feature of most cancer cells that is often accompanied by an elevated rate of chromosome mis-segregation termed chromosome instability (CIN). While CIN can act as a driver of cancer genome evolution and tumor progression, recent findings point to the existence of a threshold level beyond which CIN becomes a barrier to tumor growth and therefore can be exploited therapeutically. Drugs known to increase CIN beyond the therapeutic threshold are currently few in number, and the clinical promise of targeting the CIN phenotype warrants new screening efforts. However, none of the existing methods, including the in vitro micronuclei (MNi) assay, developed to quantify CIN, is entirely satisfactory.
methodsWe have developed a new assay for measuring CIN. This quantitative assay for chromosome mis-segregation is based on the use of a non-essential human artificial chromosome (HAC) carrying a constitutively expressed EGFP transgene. Thus, cells that inherit the HAC display green fluorescence, while cells lacking the HAC do not. This allows the measurement of HAC loss rate by routine flow cytometry.
resultsUsing the HAC-based chromosome loss assay, we have analyzed several well-known anti-mitotic, spindle-targeting compounds, all of which have been reported to induce micronuclei formation and chromosome loss. For each drug, the rate of HAC loss was accurately measured by flow cytometry as a proportion of non-fluorescent cells in the cell population which was verified by FISH analysis. Based on our estimates, despite their similar cytotoxicity, the analyzed drugs affect the rates of HAC mis-segregation during mitotic divisions differently. The highest rate of HAC mis-segregation was observed for the microtubule-stabilizing drugs, taxol and peloruside A.
conclusionThus, this new and simple assay allows for a quick and efficient screen of hundreds of drugs to identify those affecting chromosome mis-segregation. It also allows ranking of compounds with the same or similar mechanism of action based on their effect on the rate of chromosome loss. The identification of new compounds that increase chromosome mis-segregation rates should expedite the development of new therapeutic strategies to target the CIN phenotype in cancer cells.
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