chromosome instability (cin), or continual changes in chromosome complements, is an enabling feature of cancer; however, the molecular determinants of cin remain largely unknown. emerging data now suggest that aberrant sister chromatid cohesion may induce cin and contribute to cancer. to explore this possibility, we employed clinical and fundamental approaches to systematically assess the impact reduced cohesion gene expression has on cin and cancer. ten genes encoding critical functions in cohesion were evaluated and remarkably, each exhibits copy number losses in 12 common cancer types, and reduced expression is associated with worse patient survival. to gain mechanistic insight, we combined siRnA-based silencing with single cell quantitative imaging microscopy to comprehensively assess the impact reduced expression has on cin in two karyotypically stable cell lines. We show that reduced expression induces cin phenotypes, namely increases in micronucleus formation and nuclear areas. Subsequent direct tests involving a subset of prioritized genes also revealed significant changes in chromosome numbers with corresponding increases in moderate and severe cohesion defects within mitotic chromosome spreads. Collectively, our clinical and fundamental findings implicate reduced sister chromatid cohesion, resulting from gene copy number losses, as a key pathogenic event in the development and progression of many cancer types.

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There were no significant differences between AAA and controls at baseline, aside from higher rates peripheral vascular disease and younger age in the control group (P < .01). There was significantly greater inflammation found in AAA tissue compared with control (P < .00001). There was also significantly higher CD68þ macrophages counts in ILT-rich regions compared with control (P < .0001); however, there was no difference in MMP-12 or IL-6 levels between ILT and non-ILT regions, and no correlation between ILT thickness and MMP-12 levels. Conclusions: Although we demonstrated inflammation and increased CD68þ macrophage levels adjacent to ILT in AAA compared with control, contrary to our hypothesis there was no difference in macrophagerelated elastases and cytokines, suggesting that macrophages may have a limited role in AAA degeneration. We did, however, notice a trend toward higher levels of interleukin in thrombus containing regions compared with nonthrombus regions and control tissues, suggesting that perhaps macrophage activity may be elevated in the thrombus containing regions of the AAA that tends to rupture.