Frequent loss of expression without sequence mutations of the DCC gene in primary gastric cancer

Loss of heterozygosity (LOH) on chromosome 18q21 is frequently found in var ious human cancers, suggesting the presence of tumour suppressor gene(s) in this chromosomal region. DCC is the most likely target of LOH because loss or reduction of DCC expression has been found in many types of cancers. Ho wever, few reports have focused on sequence mutations of this gene. We inve stigated sequence mutations and expression of DCC in primary gastric cancer s. We studied mutations in 25 of the 29 DCC exons by PCR-SSCP in 17 primary gastric cancers exhibiting LOH on 18q21. No mutations of DCC were found in any of the tumours, although 78% (47/60) of the primary tumours showed app arent loss or reduction of DCC expression by immunohistochemistry. Analysis of methylation status of DCC revealed that methylation frequently occurred in both primary tumours (75%; 45/60) and corresponding non-cancerous gastr ic mucosae (72%; 43/60). Methylated status of DCC was significantly correla ted with the loss of DCC expression in primary tumours (P < 0.01). These re sults indicate that DCC is frequently silenced, probably by epigenetic mech anisms instead of sequence mutations in gastric cancer. (C) 2001 Cancer Res earch Campaign http://www.bjcancer.com.