A new assay for measuring chromosome instability (CIN) and identification of drugs that elevate CIN in cancer cells

Hee-Sheung Lee, Nicholas CO Lee, Brenda R Grimes, Alexander Samoshkin, Artem V Kononenko, Ruchi Bansal, Hiroshi Masumoto, William C Earnshaw, Natalay Kouprina, Vladimir Larionov

Aneuploidy 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.