Journal
HISTOPATHOLOGY
Volume 58, Issue 5, Pages 660-668Publisher
WILEY-BLACKWELL
DOI: 10.1111/j.1365-2559.2011.03819.x
Keywords
chromodomain helicase DNA-binding proteins; colorectal cancer; gastric cancer; microsatellite instability; mutation
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Funding
- KOSEF [R01-2008-000-10014-0]
- Ministry for Health, Welfare & Family Affairs, Republic of Korea [A092258]
- National Research Foundation of Korea [R01-2008-000-10014-0] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Aims: Chromodomain helicase DNA-binding protein (CHD) is a regulator of the chromatin remodelling process. The aim was to determine the CHD1, CHD2, CHD3, CHD4, CHD7, CHD8 and CHD9mutational status of mononucleotide repeats in gastric and colorectal cancers with microsatellite instability (MSI). Methods and Results: The repeats were determined in 28 gastric cancers (GCs) with high MSI (MSI-H), 45 GCs with low MSI (MSI-L)/stable MSI (MSS), 35 colorectal cancers (CRCs) with MSI-H and 45 CRCs with MSI-L/MSS by single-strand conformation polymorphism analysis. CHD4 and CHD8 expressionwas also examined in GCs and CRCs by immunohistochemistry. CHD1, CHD2, CHD3, CHD4, CHD7, CHD8 and CHD9 mutations were found in five, 19, three, five, seven, 10 and seven cancers, respectively. They were detected in MSI-H cancers, but not in MSI-L/MSS cancers. Loss of CHD4 expression was observed in 56.4% of the GCs and 55.7% of the CRCs, and loss of CHD8 was observed in 35.7% of the GCs and 28.6% of the CRCs. The cancers with CHD4 and CHD8 mutations showed loss of CHD4 and CHD8 expression, respectively. Conclusions: Frameshift mutation and loss of expression of CHD genes are common in GCs and CRCs with MSI-H.These alterations might contribute to cancer pathogenesis by deregulating CHD-mediated chromatin remodelling.
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