Hypomethylation of DNA in tumor cells is associated with genomic instability and has been suggested to be due to activation of mitotic recombination. We have studied the methylation patterns in two 650 kb double minute chromosomes present in two mouse tumor cell lines, resistant to methotrexate. Multiple copies of the double minute chromosomes amplifying the dihydrofolate reductase gene are pre...

MYC dysregulation initiates a dynamic process of genomic instability that is linked to tumor initiation. Early studies using MYC-carrying retroviruses showed that these viruses were potent transforming agents. Cell culture models followed that addressed the role of MYC in transformation. With the advent of MYC transgenic mice, it became obvious that MYC deregulation alone was sufficient to init...

Cellular aging in Saccharomyces cerevisiae can lead to genomic instability and impaired mitotic asymmetry. To investigate the role of oxidative stress in cellular aging, we examined the effect of exogenous hydrogen peroxide on genomic instability and mitotic asymmetry in a collection of yeast strains with diverse backgrounds. We treated yeast cells with hydrogen peroxide and monitored the chang...

Chronic hepatitis B virus (HBV) infection is an important cause of hepatocellular carcinoma (HCC) worldwide, especially in Asia. HBV induces HCC through multiple oncogenic pathways. Hepatitis-induced hepatocyte inflammation and regeneration stimulates cell proliferation. The interplay between the viral and host factors activates oncogenic signaling pathways and triggers cell transformation. In ...

Genomic instability, the propensity of aberrations in chromosomes, plays a critical role in the development of many diseases. High throughput genotyping experiments have been performed to study genomic instability in diseases. The output of such experiments can be summarized as high dimensional binary vectors, where each binary variable records aberration status at one marker locus. It is of ke...

Over the past 15 years, pluripotent cells, either embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs), became a formidable cellular platform to study developmental biology, model disease in vitro and pursue new drug discoveries. Furthermore, the promise of using endless cell derivatives from pluripotent cells to treat incurable diseases such as diabetes, neurodegenerative or h...

© Springer International Publishing Switzerland 2015 C. Maxwell, C. Roskelley (eds.), Genomic Instability and Cancer Metastasis, Cancer Metastasis Biology and Treatment 20, DOI 10.1007/978-3-319-12136-9_7 C. M. Nelson () · A. K. Simi · A. S. Piotrowski Department of Chemical & Biological Engineering, Princeton University, 303 Hoyt Laboratory, William Street, Princeton, NJ 08544, USA e-mail: ce...

Mitochondrial dysfunction and oxidative stress have been implicated in cellular senescence, apoptosis, aging and aging-associated pathologies. Telomere shortening and genomic instability have also been associated with replicative senescence, aging and cancer. Here we show that mitochondrial dysfunction leads to telomere attrition, telomere loss, and chromosome fusion and breakage, accompanied b...

Septins are highly conserved cytoskeletal GTP-binding proteins implicated in numerous cellular processes from apoptosis to vesicle trafficking. Septins have been associated with leukemia and solid tumor malignancies, including breast, ovarian, and prostate. We previously reported that high SEPT9_i1 expression in human mammary epithelial cell lines (HMECs) led to malignant cellular phenotypes su...