During tumorigenesis, cells acquire immortality in association with the development of genomic instability. However, it is still elusive how genomic instability spontaneously generates during the process of tumorigenesis. Here, we show that precancerous DNA lesions induced by oncogene acceleration, which induce situations identical to the initial stages of cancer development, trigger tetraploid...

The carcinogenic process is multistep in terms of its etiology and multifactor in terms of its evolution. In this context, the temporal accumulation of multiple genetic changes during multistage carcinogenesis that can be mediated at least in part by genomic instability may represent crucial components of tumor cell evolution. Evidence is accumulating indicating a close link between genomic ins...

Previously, we reported that the progeny of mammalian cells, which has been exposed to sodium arsenite for two cell cycles, exhibited chromosomal instability and concurrent DNA hypomethylation, when they were subsequently investigated after two months of subculturing (about 120 cell generations) in arsenite-free medium. In this work, we continued our investigations of the long-lasting arsenite-...

The discovery of induced pluripotent stem cells(iPSCs) is a promising advancement in the field of regenerative medicine. Previous studies have indicated that the teratoma-forming propensity of iPSCs is variable; however, the relationship between tumorigenic potential and genomic instability in human iPSCs (HiPSCs) remains to be fully elucidated. Here, we evaluated the malignant potential of HiP...

DNA hypomethylation is a common trait of colorectal cancer. Studies in tumor cell lines and animal models indicate that genome-wide demethylation may cause genetic instability and hence facilitate or accelerate tumor progression. Recent studies have shown that DNA hypomethylation precedes genomic damage in human gastrointestinal cancer, but the nature of this damage has not been clearly establi...

Inflammatory bowel disease (IBD) and polyps, are common colorectal pathologies in western society and are risk factors for development of colorectal cancer (CRC). Genomic instability is a cancer hallmark and is connected to changes in chromosomal structure, often caused by double strand break formation (DSB), and aneuploidy. Cellular stress, may contribute to genomic instability. In colorectal ...

Global hypomethylation in white blood cell (WBC) DNA has recently been proposed as a potential biomarker for determining cancer risk through genomic instability. However, the amplitude of the changes associated with age and the impacts of environmental factors on DNA methylation are unclear. In this study, we investigated the association of genomic hypomethylation with age, cigarette use, drink...

Genetic, or genomic, instability refers to a series of observed spontaneous genetic changes occurring at an accelerated rate in cell populations derived from the same ancestral precursor. This is far from a new finding, but is one that has increasingly gained more attention in the last decade due to its plausible role(s) in tumorigenesis. The majority of genetic alterations contributing to the ...

Diffuse large B-cell lymphoma is the most common lymphoid malignancy in adults. It is a heterogeneous disease with variability in outcome. Genomic instability of a subset of proto-oncogenes, including c-MYC, BCL6, RhoH, PIM1, and PAX5, can contribute to initial tumor development and has been correlated with poor prognosis and aggressive tumor growth. Lymphomas in which these proto-oncogenes are...

Genomic instability refers to an increased tendency of alterations in the genome during the life cycle of cells. It is a major driving force for tumorigenesis. During a cell division, genomic instability is minimized by four major mechanisms: high-fidelity DNA replication in S-phase, precise chromosome segregation in mitosis, error free repair of sporadic DNA damage, and a coordinated cell cycl...