Abstract | BACKGROUND AND AIMS: METHODS: We genotyped small bowel biopsies and peripheral blood samples from 20 untreated CD patients using five microsatellites related to MMR genes (panel A), and five repeats associated with tumor suppressor genes, chromosome instability, inflammation, and cancer (panel B). RESULTS:
Genomic instability was found in seven out of 20 (35%) cases at: D5S107, D18S58, GSTP, TP53 or DCC, being TP53 the most frequently affected (five out of seven cases; 71%). Microsatellite alterations were significantly found using panel B markers (P=0.04). No cases with high frequency of MSI and replication error phenotype were detected. Only one case displayed MSI-L alone. Three patients exhibited LOH and three other cases showed LOH with low level of MSI, being classified as having chromosome instability phenotype. CONCLUSION: Two novel observations were found in this study: first, the finding that non-neoplastic cells from a group of untreated CD patients present genomic instability at nucleotide level; and second, the advantage to use carefully selected microsatellites to identify celiac patients with molecular instability. Our data support the existence of chromosome instability phenotype in CD, suggesting that stable and unstable patients are genomically distinct subtypes that may follow a different evolution.
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Authors | Ariela F Fundia, Alejandra S Cottliar, Graciela La Motta, Adriana Crivelli, Juan Carlos Gómez, Irma R Slavutsky, Irene B Larripa |
Journal | European journal of gastroenterology & hepatology
(Eur J Gastroenterol Hepatol)
Vol. 20
Issue 12
Pg. 1159-66
(Dec 2008)
ISSN: 1473-5687 [Electronic] England |
PMID | 18946361
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Adult
- Aged
- Celiac Disease
(genetics)
- Female
- Genetic Markers
- Genomic Instability
- Genotype
- Humans
- Loss of Heterozygosity
- Male
- Microsatellite Instability
- Microsatellite Repeats
- Middle Aged
- Nutritional Status
- Young Adult
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