Hypo-methylation mediates chromosomal instability in pancreatic NET

Mechanisms of Chromosomal Instability

Most solid tumors are aneuploid, having a chromosome number that is not a multiple of the haploid number, and many frequently mis-segregate whole chromosomes in a phenomenon called chromosomal instability (CIN). CIN positively correlates with poor patient prognosis, indicating that reduced mitotic fidelity contributes to cancer progression by increasing genetic diversity among tumor cells. Here...

Trans-chromosomal methylation

The epigenome plays a vital role in helping to maintain and regulate cell functions in all organisms. Alleles with differing epigenetic marks in the same nucleus do not function in isolation but can interact in trans to modify the epigenetic state of one or both alleles. This is particularly evident when two divergent epigenomes come together in a hybrid resulting in thousands of alterations to...

Estrogen mediates Aurora-A overexpression, centrosome amplification, chromosomal instability, and breast cancer in female ACI rats.

Estrogens play a crucial role in the causation and development of sporadic human breast cancer (BC). Chromosomal instability (CIN) is a defining trait of early human ductal carcinoma in situ (DCIS) and is believed to precipitate breast oncogenesis. We reported earlier that 100% of female ACI (August/Copenhagen/Irish) rats treated with essentially physiological serum levels of 17beta-estradiol l...

FAT10 mediates the effect of TNF-α in inducing chromosomal instability.

Tumor necrosis factor-alpha (TNF-α) plays important roles in chronic inflammation-associated tumorigenesis but the mechanisms involved remain poorly understood. Previously, we reported that high levels of FAT10 led to chromosomal instability that is mediated by an abbreviated mitotic phase. Here, we show that TNF-α induces FAT10 gene expression through TNF receptor 1 (TNFR1) and activates the N...

Mouse Models for Chromosomal Instability