Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer

Leach, Fredrick S.; Nicolaides, Nicholas C.; Papadopoulos, Nickolas; Liu, Bo; Jen, Jin; Parsons, Ramon; Peltomäki, Païvi; Sistonen, Pertti; Aaltonen, Lauri A.; Nyström‐Lahti, Minna; Guan, Xin Yuan; Zhang, Ji; Meltzer, Paul S.; Yu, Jing; Kao, Fa Ten; Chen, David J.; Cerosaletti, Karen; Fournier, R. E. K.; Todd, S.; Lewis, Tracey; Leach, Robin J.; Naylor, Susan L.; Weissenbach, Jean; Mecklin∥, Jukka–Pekka; Järvinen, Heikki; Petersen, Gloria M.; Hamilton, Stanley R.; Green, Jane; Jass, Jeremy R.; Watson, Patrice; Lynch, Henry T.; Trent, Jeffrey M.; Chapelle, Albert de la; Kinzler, Kenneth W.; Vogelstein, Bert

doi:10.1016/0092-8674(93)90330-s

Cited by 2,041 publications

(889 citation statements)

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“…This phenomenon has been shown to be a frequent, if not obligatory, surrogate marker of underlying functional inactivation of one of the human DNA mismatch repair (MMR) genes. [1][2][3][4][5][6] Functional loss of a MMR gene occurs due to biallelic inactivation via some combination of coding region mutation, loss of heterozygosity (LOH), and/or promoter methylation. 7,8 Germline mutation of a MMR gene has been shown to be the autosomal dominant genetic defect in most hereditary nonpolyposis colon cancer (HNPCC) kindreds.…”

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Detection of Microsatellite Instability by Fluorescence Multiplex Polymerase Chain Reaction

Berg

Glaser

Thompson

et al. 2000

The Journal of Molecular Diagnostics

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We have created a clinical molecular diagnostic assay to test for microsatellite instability (MSI) at multiple loci simultaneously in paraffin-embedded surgical pathology colon resection specimens. This fluorescent multiplex polymerase chain reaction (PCR) assay analyzes the five primary microsatellite loci recommended at the 1997 National Cancer Institute-sponsored conference on MSI for the identification of MSI or replication errors in colorectal cancer: Bat-25, Bat-26, D2S123, D5S346, and D17S250. Amplicon detection is accomplished by capillary electrophoresis using the ABI 310 Genetic Analyzer. Assay validation compared 18 specimens previously assessed by radioactive PCR and polyacrylamide gel electrophoresis detection to results generated by the reported assay. Germline and tumor DNA samples were amplified in separate multiplex PCR reactions, sized in separate capillary electrophoresis runs, and compared directly to identify novel length alleles in tumor tissue. A concordance of 100% between the two modalities was achieved. The multiplex assay routinely detected a subpopulation of 10% tumor alleles in the presence of 90% normal alleles. A novel statistical model was generated that corroborates the validity of using results generated by analysis of five independent microsatellites to achieve a single overall MSI diagnosis. The assay presented is superior to standard radioactive monoplex PCR, polyacrylamide gel electrophoretic analysis, primarily due to the multiplex PCR format. (J Mol Diag 2000, 2:20 -28)Microsatellite instability (MSI), or replication error, is a manifestation of genomic instability arising in a variety of human neoplasms where tumor cells have a decreased overall ability to faithfully replicate DNA. This phenomenon has been shown to be a frequent, if not obligatory, surrogate marker of underlying functional inactivation of one of the human DNA mismatch repair (MMR) genes. [1][2][3][4][5][6]

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confidence: 99%

Detection of Microsatellite Instability by Fluorescence Multiplex Polymerase Chain Reaction

Berg

Glaser

Thompson

et al. 2000

The Journal of Molecular Diagnostics

Self Cite

139

121

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“…This model has been actually con®rmed by the ®nding that the hereditary nonpolyposis colorectal cancer (HNPCC) is associated with defects in genes coding for homologues of the bacterial mismatch repair proteins MutS or MutL (Fishel et al, 1993;Leach et al, 1993;Parsons et al, 1993;Jiricny, 1994; Edelman et al, 1997). Indeed, cells from these tumours have a hypermutator phenotype and the biochemical defect in the mismatch repair process was established (Bronner et al, 1994;Richards et al, 1997).…”

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Mutations in OGG1, a gene involved in the repair of oxidative DNA damage, are found in human lung and kidney tumours

et al. 1998

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The human OGG1 gene encodes a DNA glycosylase activity catalysing the excision of the mutagenic lesion 7,8-dihydro-8-oxoguanine from oxidatively damaged DNA. The OGG1 gene was localized to chromosome 3p25, a region showing frequent loss of heterozygosity (LOH) in lung and kidney tumours. In this study, we have analysed by RT ± PCR the expression of OGG1 in 25 small cell lung cancers, in 15 kidney carcinomas and the 15 normal kidney counterparts. The results show that OGG1 messenger RNA can be detected in all tumours tested and that no signi®cant di erence was observed in the level of expression between normal and tumoral kidney tissues. Denaturing gradient gel electrophoresis (DGGE) was used to screen this series of human tumours for alterations in the OGG1 cDNA. The study revealed homozygous mutations in three tumours, two from lung and one from kidney. Sequencing analysis of the mutants identi®ed a single base substitution in each of the three cases: two tranversions (GC to TA and TA to AT) and one transition (GC to AT). All three substitutions cause an amino acid change in the hOgg1 protein. For the mutant kidney tumour, the normal tissue counterpart shows a wild-type pro®le. These results suggest a role for OGG1 mutations in the course of the multistage process of carcinogenesis in lung or kidney.Keywords: oxidative DNA damage; DNA repair; missense mutations of OGG1 gene; human lung and kidney cancer; tumour suppressor gene Damage to DNA by oxygen-free radicals is postulated to cause mutations that are associated with the initiation or the progression of human cancers (Breimer, 1990;Loeb, 1997;Beckman and Ames, 1997). Oxidative damage-induced mutations can activate oncogenes or inactivate tumour suppressor genes altering the cell growth control (Fearon, 1997). An oxidatively damaged guanine, 7,, is abundantly produced in DNA as a consequence of the cellular oxidative metabolism or the exposure to ionizing radiation or chemical carcinogens (Dizdaroglu, 1991;Cadet et al., 1997). The presence of 8-OxoG in DNA has been shown to be mutagenic since, while this lesion does not impede DNA chain elongation, it preferentially pairs with adenine during in vitro DNA synthesis (Shibutani et al., 1991). The biological incidence of the presence of 8-OxoG in DNA has been unveiled by the study of two genes in E. coli, fpg (mutM) and mutY (micA) which code for DNA glycosylases that cooperate to prevent the mutagenic e ects of 8-OxoG in DNA (Boiteux et al., 1987;Cabrera et al., 1988;Radicella et al., 1988;Nghiem et al., 1988;Au et al., 1989). Inactivation of either gene leads to a spontaneous mutator phenotype characterized by the exclusive increase in GC to TA transversions (Michaels and Miller, 1992;Grollman and Moriya, 1993;Boiteux and Laval, 1997). In Saccharomyces cerevisiae the OGG1 gene was cloned as the functional eukaryotic homologue of the bacterial fpg gene (Au ret van der Kemp et al., 1996). The yeast Ogg1 protein is a DNA glycosylase/AP lyase which excises 8-OxoG, formamidopyrimidines and incizes apurinic/apyrimid...

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“…They accumulate frequent deletions and insertions in microsatellite DNA sequences due to de®cient repair of spontaneous errors which occur during the replication of these repetitive DNA sequences Thibodeau et al, 1993;Ionov et al, 1993). The MSI-H phenotype is associated with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome as a result of predisposing constitutional mutations in genes involved in DNA mismatch repair (Bronner et al, 1994;Papadopoulos et al, 1994;Fishel et al, 1993;Leach et al, 1993). The MSI-H phenotype is also observed in about 15% of sporadic colon, gastric and endometrial carcinomas.…”

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Variable mutation frequencies in coding repeats of TCF-4 and other target genes in colon, gastric and endometrial carcinoma showing microsatellite instability

et al. 1999

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Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer

Cited by 2,041 publications

References 46 publications

Detection of Microsatellite Instability by Fluorescence Multiplex Polymerase Chain Reaction

Detection of Microsatellite Instability by Fluorescence Multiplex Polymerase Chain Reaction

Mutations in OGG1, a gene involved in the repair of oxidative DNA damage, are found in human lung and kidney tumours

Variable mutation frequencies in coding repeats of TCF-4 and other target genes in colon, gastric and endometrial carcinoma showing microsatellite instability

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