High epithelial and stromal genetic instability of chromosome 17 in ulcerative colitis-associated carcinogenesis.
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.
Matsumoto
Naoko
N
Department of Pathology, Kitasato University School of Medicine, Kitasato 1-15-1, Sagamihara, Kanagawa 228-8555, Japan.
Yoshida
Tsutomu
T
Okayasu
Isao
I
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D002352:Carrier Proteins; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D003093:Colitis, Ulcerative / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D016158:Genes, p53; D042822:Genomic Instability; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009154:Mutation; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein