Abstract
To define the relative frequencies of genetic instability in stromal and epithelial compartments during ulcerative colitis (UC)-associated tumorigenesis, samples from laser-captured microdissection were assessed for microsatellite instability and loss of heterozygosity in regenerative tissue, dysplasia, and carcinomas in long-standing UC cases. Five National Cancer Institute-recommended standard markers and four markers located close to p53 and BRCA1 genes in chromosome 17 were tested, and p53 gene sequencing was also carried out. Although chromosome 17-MSI and -loss of heterozygosity in epithelium correlated with histological progression, in stroma they showed a consistently high frequency throughout the different stages, indicating a distinct carcinogenesis pathway of UC. The rates for standard markers were lower in both epithelium and stroma.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Adult
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Carrier Proteins
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Chromosomes, Human, Pair 17 / genetics*
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Colitis, Ulcerative / complications
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Colitis, Ulcerative / genetics*
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Colitis, Ulcerative / metabolism
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Colitis, Ulcerative / pathology
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Colorectal Neoplasms / etiology
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Colorectal Neoplasms / genetics*
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Colorectal Neoplasms / metabolism
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Colorectal Neoplasms / pathology
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DNA-Binding Proteins*
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Epithelial Cells / metabolism
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Epithelial Cells / pathology
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Genes, p53
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Genomic Instability*
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Humans
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Loss of Heterozygosity
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Microsatellite Repeats
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Middle Aged
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MutL Protein Homolog 1
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MutS Homolog 2 Protein
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Mutation
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / genetics
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Nuclear Proteins
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Proto-Oncogene Proteins / biosynthesis
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Proto-Oncogene Proteins / genetics
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Stromal Cells / metabolism
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Stromal Cells / pathology
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Tumor Suppressor Protein p53 / biosynthesis
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Tumor Suppressor Protein p53 / genetics
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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DNA-Binding Proteins
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MLH1 protein, human
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Neoplasm Proteins
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Nuclear Proteins
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Proto-Oncogene Proteins
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Tumor Suppressor Protein p53
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MSH2 protein, human
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MutL Protein Homolog 1
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MutS Homolog 2 Protein