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T Toyota - One of the best experts on this subject based on the ideXlab platform.
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Relationship between Microsatellite Instability and telomere shortening in colorectal cancer.
Diseases of the colon and rectum, 2000Co-Authors: S Takagi, Y Kinouchi, N Hiwatashi, F Nagashima, M Chida, S Takahashi, K Negoro, T Shimosegawa, T ToyotaAbstract:Two pathways have been proposed for the development of colorectal cancers: loss of heterozygosity and replication error. Colorectal cancers arising through the replication error pathway, like most hereditary nonpolyposis colorectal cancers, show Microsatellite Instability. It has been also reported that telomere shortening frequently occurs in colorectal cancers and that telomerase is often activated strongly in them. The aim of this study was to examine whether any relationships can be found among Microsatellite Instability, telomere length, and telomerase activity in colorectal cancers. Genomic DNA was extracted from 55 invasive cancers and corresponding normal mucosas. Five Microsatellite loci were analyzed by polymerase chain reaction. Telomere length was examined by Southern blot analysis. Telomerase activity was assayed by telomeric repeat amplification protocol with minor modifications. Microsatellite Instability was found in 8 (14.5 percent) of 55 tumors, and all of them showed short telomeres. Furthermore, four high-frequency Microsatellite Instability tumors that showed Microsatellite Instability at more than two loci exhibited remarkably short telomeres. The Microsatellite Instability correlated significantly with frequency of telomere shortening (P = 0.0183; Fisher's exact probability test), but not with strength of telomerase activity. The relationship identified by this study between Microsatellite Instability and telomere shortening might suggest some association between the DNA mismatch repair system and the telomere maintenance mechanism in colorectal cancers.
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Relationship between Microsatellite Instability and telomere shortening in colorectal cancer.
Diseases of the Colon & Rectum, 2000Co-Authors: S Takagi, Y Kinouchi, N Hiwatashi, F Nagashima, M Chida, S Takahashi, K Negoro, T Shimosegawa, T ToyotaAbstract:PURPOSE: Two pathways have been proposed for the development of colorectal cancers: loss of heterozygosity and replication error. Colorectal cancers arising through the replication error pathway, like most hereditary nonpolyposis colorectal cancers, show Microsatellite Instability. It has been also reported that telomere shortening frequently occurs in colorectal cancers and that telomerase is often activated strongly in them. The aim of this study was to examine whether any relationships can be found among Microsatellite Instability, telomere length, and telomerase activity in colorectal cancers. METHODS: Genomic DNA was extracted from 55 invasive cancers and corresponding normal mucosas. Five Microsatellite loci were analyzed by polymerase chain reaction. Telomere length was examined by Southern blot analysis. Telomerase activity was assayed by telomeric repeat amplification protocol with minor modifications. RESULTS: Microsatellite Instability was found in 8 (14.5 percent) of 55 tumors, and all of them showed short telomeres. Furthermore, four high-frequency Microsatellite Instability tumors that showed Microsatellite Instability at more than two loci exhibited remarkably short telomeres. The Microsatellite Instability correlated significantly with frequency of telomere shortening (P=0.0183; Fisher's exact probability test), but not with strength of telomerase activity. CONCLUSION: The relationship identified by this study between Microsatellite Instability and telomere shortening might suggest some association between the DNA mismatch repair system and the telomere maintenance mechanism in colorectal cancers.
Wade S. Samowitz - One of the best experts on this subject based on the ideXlab platform.
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Microsatellite Instability and colorectal cancer.
Archives of pathology & laboratory medicine, 2011Co-Authors: Katherine B. Geiersbach, Wade S. SamowitzAbstract:Context.—About 15% of colorectal cancers are characterized by genomic Microsatellite Instability, and of these, about 1 in 5 (2%–4% overall) are due to Lynch syndrome, a dominantly inherited condition predisposing the patient to cancers of multiple organ systems, including the gastrointestinal tract. Identification of individuals with Lynch syndrome allows for increased surveillance of the affected individual and of potentially affected family members. Objective.—To review the literature on Microsatellite Instability in colorectal cancer and current laboratory diagnostic testing strategies for the detection of Lynch syndrome. Data Sources.—This review is based on peer-reviewed literature, published guidelines from professional organizations (Evaluation of Genomic Applications in Practice and Prevention Working Group, National Comprehensive Cancer Network), and information from clinical laboratories performing Microsatellite Instability testing. Conclusions.—Universal screening for Lynch syndrome in all in...
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Microsatellite Instability in colorectal adenomas
Gastroenterology, 1997Co-Authors: Wade S. Samowitz, Martha L. SlatteryAbstract:BACKGROUND & AIMS: Microsatellite Instability in apparently sporadic, predominantly right-sided colon cancers seems to be the result of an acquired, rather than germline, genetic change that impairs mismatch repair. The timing of this change with respect to the adenomacarcinoma sequence has not been determined. The aim of this study was to evaluate colonic adenomatous polyps for Microsatellite Instability to determine whether Instability reflects an early genetic change in colonic neoplasia. METHODS: Ninety-three sporadic colonic adenomas (44 right- sided and 49 left-sided) from 48 individuals were evaluated for Microsatellite Instability with a set of 10 polymerase chain reaction primer sets. RESULTS: Eighty percent of adenomatous polyps showed no Instability. Ninety-eight percent showed Instability with
S Takagi - One of the best experts on this subject based on the ideXlab platform.
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Relationship between Microsatellite Instability and telomere shortening in colorectal cancer.
Diseases of the colon and rectum, 2000Co-Authors: S Takagi, Y Kinouchi, N Hiwatashi, F Nagashima, M Chida, S Takahashi, K Negoro, T Shimosegawa, T ToyotaAbstract:Two pathways have been proposed for the development of colorectal cancers: loss of heterozygosity and replication error. Colorectal cancers arising through the replication error pathway, like most hereditary nonpolyposis colorectal cancers, show Microsatellite Instability. It has been also reported that telomere shortening frequently occurs in colorectal cancers and that telomerase is often activated strongly in them. The aim of this study was to examine whether any relationships can be found among Microsatellite Instability, telomere length, and telomerase activity in colorectal cancers. Genomic DNA was extracted from 55 invasive cancers and corresponding normal mucosas. Five Microsatellite loci were analyzed by polymerase chain reaction. Telomere length was examined by Southern blot analysis. Telomerase activity was assayed by telomeric repeat amplification protocol with minor modifications. Microsatellite Instability was found in 8 (14.5 percent) of 55 tumors, and all of them showed short telomeres. Furthermore, four high-frequency Microsatellite Instability tumors that showed Microsatellite Instability at more than two loci exhibited remarkably short telomeres. The Microsatellite Instability correlated significantly with frequency of telomere shortening (P = 0.0183; Fisher's exact probability test), but not with strength of telomerase activity. The relationship identified by this study between Microsatellite Instability and telomere shortening might suggest some association between the DNA mismatch repair system and the telomere maintenance mechanism in colorectal cancers.
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Relationship between Microsatellite Instability and telomere shortening in colorectal cancer.
Diseases of the Colon & Rectum, 2000Co-Authors: S Takagi, Y Kinouchi, N Hiwatashi, F Nagashima, M Chida, S Takahashi, K Negoro, T Shimosegawa, T ToyotaAbstract:PURPOSE: Two pathways have been proposed for the development of colorectal cancers: loss of heterozygosity and replication error. Colorectal cancers arising through the replication error pathway, like most hereditary nonpolyposis colorectal cancers, show Microsatellite Instability. It has been also reported that telomere shortening frequently occurs in colorectal cancers and that telomerase is often activated strongly in them. The aim of this study was to examine whether any relationships can be found among Microsatellite Instability, telomere length, and telomerase activity in colorectal cancers. METHODS: Genomic DNA was extracted from 55 invasive cancers and corresponding normal mucosas. Five Microsatellite loci were analyzed by polymerase chain reaction. Telomere length was examined by Southern blot analysis. Telomerase activity was assayed by telomeric repeat amplification protocol with minor modifications. RESULTS: Microsatellite Instability was found in 8 (14.5 percent) of 55 tumors, and all of them showed short telomeres. Furthermore, four high-frequency Microsatellite Instability tumors that showed Microsatellite Instability at more than two loci exhibited remarkably short telomeres. The Microsatellite Instability correlated significantly with frequency of telomere shortening (P=0.0183; Fisher's exact probability test), but not with strength of telomerase activity. CONCLUSION: The relationship identified by this study between Microsatellite Instability and telomere shortening might suggest some association between the DNA mismatch repair system and the telomere maintenance mechanism in colorectal cancers.
Akiyoshi T - One of the best experts on this subject based on the ideXlab platform.
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The heterogeneity of Microsatellite Instability in multiple gastric cancers.
The American journal of gastroenterology, 1995Co-Authors: H Nakashima, H Inoue, M Mori, H Ueo, Masayuki Honda, Kenji Shibuta, Arinaga S, Era S, Akiyoshi TAbstract:To obtain a better understanding of the role of genetic Instability in developing gastric cancer, it is of great interest to examine Microsatellite alterations in synchronous multiple gastric cancers that are thought may have the same genetic background and the same microenvironment of the stomach. We report our experience with two patients with synchronous multiple gastric cancers; patient 1 showed two carcinomas in the stomach, whereas patient 2 showed two carcinomas and two adenomas in the stomach. We examined the DNAs from the two cases for Microsatellite Instability and expected that the status of Microsatellite Instability in each tumor from the same stomach would be the same. However, patient 2 revealed heterogeneity in the Microsatellite Instability, i.e., an early cancer that showed some apparent alterations, whereas the other advanced cancer and two adenomas did not. On the other hand, neither of the two carcinomas in patient 1 showed Microsatellite Instability. To our knowledge, there has been no previous report of Microsatellite Instability in multiple gastric cancers. In this report, we describe a case that revealed such a heterogeneity of the Microsatellite Instability, in which the carcinogenic process of each tumor may undergo different genetic alterations even under the same genetic conditions and background.
Keizo Sugimachi - One of the best experts on this subject based on the ideXlab platform.
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Microsatellite Instability in cancer: what problems remain unanswered?
Surgery, 2002Co-Authors: Shinya Oda, Yoshihiko Maehara, Yasushi Sumiyoshi, Keizo SugimachiAbstract:Analyses of Microsatellite Instability have been prevalent, particularly in the field of oncology. However, the literature on this subject is diverse. The discrepancies may derive from methodological problems in the conventional techniques used for analysis. Problems include low quantitativity in the detection systems, inaccurate migration in electrophoresis, and Taq polymerase-mediated modifications of polymerase chain reaction products. Indeed, use of a new fluorescent technique where these problems have been overcome has elucidated various intriguing and previously unrecognized aspects of Microsatellite Instability in human cancers. Patterns of Microsatellite changes observed in various human cancers can be classified into 2 subtypes, those showing relatively small changes within 6 base pairs (type A) and those exhibiting drastic changes over 8 base pairs (type B). Although type A Microsatellite Instability has been connected to defective mismatch repair phenotype, the relationship between type B Microsatellite Instability and defective mismatch repair phenotype remains unclear. Nevertheless, as symbolized in cases of hereditary nonpolyposis colorectal cancer, connections between type B Microsatellite Instability and familial predisposition have been suggested in some cancers. The molecular background of type B Microsatellite changes warrants particular attention.
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The Instability within: problems in current analyses of Microsatellite Instability
Mutation research, 2001Co-Authors: Yoshihiko Maehara, Shinya Oda, Keizo SugimachiAbstract:Microsatellite Instability is regarded as one of the phenotypes of defective DNA mismatch repair and, consequently, as a marker of high risk for cancer. Despite numerous studies, the reported rates for positive Microsatellite Instability differ widely in each human malignancy. These discrepancies may relate to problems in the methods used. To establish a methodology for an accurate Microsatellite Instability analysis, technical requirements for a precise assay and biological conditions required for positive Microsatellite Instability were discussed. First, to describe Microsatellite changes in detail, a sensitive detection system with linear detection characteristics and electrophoresis with standardised migration and minimised migration errors are considered to be necessary. Therefore, systems using fluorescent labelling and laser scanning are recommended. For reproducible polymerase chain reactions, it is essential to control the terminal deoxynucleotidyl transferase activity in Taq polymerase. Second, as a biological condition for positive Microsatellite Instability, feasible selection and combination of Microsatellite markers, mutations in specific DNA mismatch repair genes and existence of monoclonal populations enriched sufficiently in a sample are essential. Finally, one possible diagnostic criterion for positive Microsatellite Instability is proposed, that is the existence of one of the patterns shown in the panel (see Fig. 6) at one or more loci in a set of more than five Microsatellite markers.