Genetic and expressional alterations of CHD genes in gastric and colorectal cancers

Kim M S, Chung N G, Kang M R, Yoo N J & Lee S H
(2011) Histopathology 58 , 660–668
 Genetic and expressional alterations of CHD genes in gastric and colorectal cancers 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 CHD9 mutational 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.