1,721,031 research outputs found
DNA Tumor Viruses and Colorectal Cancer.
No full textColorectal cancers (CRCs) are characterized by forms of genomic or epigenetic instability that generate a large number of genetic variations, some of which provide the growth and survival advantages necessary for neoplastic growth. The mechanistic basis of these fundamental processes is currently unknown. Herein, we review evidence that links the human polyomavirus JC virus mechanistically with these processes in CRC. We propose a model in which JC virus is ubiquitously present in the gastrointestinal tracts of healthy people and speculate that through a process that remains to be discovered, the virus becomes activated, expresses a potent oncogene, and triggers chromosomal instability and the methylator phenotype resulting in CRC
Constraints imposed by supercoiling on in vitro amplification of polyomavirus DNA
No full textPrevious attempts to identify oncogenic polyomaviruses in human cancers have yielded conflicting results, even with the application of PCR technology. Here, it was considered whether the topological features of the polyomavirus genome interfere with efficient PCR amplification. Plasmid and SV40 DNAs were used as a model system for comparing the amplification efficiency of supercoiled, circular relaxed and linear templates. It was found that detection of circular templates required 10 times more molecules than detection of identical but linear templates. Supercoiling hindered the in vitro amplification of SV40 circles by a factor of 10, and erratic amplification of supercoiled SV40 occurred with subpicogrann amounts of template. Accordingly, topoisomerase I treatment of DNA improved the PCR detection of supercoiled SV40, significantly decreasing the number of false-negative samples. Previously described, yet controversial, polyomavirus presence in human tissues should be reconsidered and topoisomerase I-sensitive polyomavirus amplification might help to detect polyomavirus genomes in mammalian tissues
A novel model to study the in vitro effects of oxidative stress on the DNA mismatch repair system.
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JC virus DNA is present in the mucosa of the human colon and in colorectal cancers
No full textJC virus (JCV) is a polyoma virus that commonly infects humans. We have found T antigen DNA sequences of JCV in the mucosa of normal human colons, colorectal cancers, colorectal cancer xenografts raised in nude mice, and in the human colon cancer cell line SW480. A larger number of viral copies is present in cancer cells than in non-neoplastic colon cells, and sequence microheterogeneity occurs within individual colonic mucosal specimens. The improved yield of detection after treatment with topoisomerase I suggests that the viral DNA is negatively supercoiled in the human tissues. These results indicate that JCV DNA can be found in colonic tissues, which raises the possibility that this virus may play a role in the chromosomal instability observed in colorectal carcinogenesis
Comparable effects of annurca apple polyphenols and 5-AZA-2'-deoxycytidine (5-AZA-2dc) on the demethylation of tumor suppressor gene promoters in colon cancer cells.
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Genetic instability and chromosomal aberrations in colorectal cancer: A review of the current models
No full textOur understanding of the pathogenesis of cancer has undergone a revolution over the past decade. Tumors develop by the accumulation of damage to genes that regulate cell growth. Many of the genes responsible for disregulation of cell growth have been identified, as have the processes that lead to the genetic damage. One of the most important concepts that has facilitated our understanding of carcinogenesis is that of genetic or "genomic" instability, which is required to permit a sufficient amount of genetic damage to accumulate to permit the neoplastic phenotype to emerge and evolve. Two mechanisms that lead to genomic instability-one of which involves the loss of chromosomal fragments from the nucleus, and a second which is characterized by microsatellite instability-are discusse
Serrated adenomas have a pattern of genetic alterations that distinguishes them from other colorectal polyps
No full textBackground: Serrated adenomas are characterized by serrated crypts with dysplasia, and are distinguished from other polyps by their histology, but the genetic basis of serrated adenomas is unknown. We investigated genetic alterations in colorectal polyps to determine if a specific pattern were associated with serrated adenomas.
Methods: Sixty-six small (< 10 mm) colorectal polyps were studied, including 11 hyperplastic polyps, 27 serrated adenomas, 9 tubular adenomas, 6 tubulovillous adenomas, and 3 villous adenomas. Allelic imbalance and microsatellite instability were detected by analysis of microsatellites on 5q, 18q, 17p, 2p, and 3p; K-ras mutations were detected by oligonucleotide hybridization.
Results: Each polyp subset had its own characteristic mutational signature. Allelic imbalance of 18q was significantly more common (P < 0.05), whereas allelic imbalance of 5q and K-ras mutations were significantly less common (P < 0.05) in serrated adenomas compared with other polyps. Allelic imbalance of 17p was not found in any polyp.
Conclusions: Serrated adenomas are significantly more likely to have allelic imbalance at 18q than other types of adenomas, and significantly less likely to have allelic imbalance at 5q or K-ras mutations. Serrated adenomas seem to evolve through a different genetic pathway than other types of polyps in the colon
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