Early Loss of Deleted in Colorectal Carcinoma Gene Transcript Detected in a Group of Benign Colon Adenomas

Abstract

We examined the expression of the putative tumor suppressor gene deleted in colorectal carcinoma (DCC) in human colon adenoma tissues and cell lines. One allele of DCC is deleted in 70% of human colon carcinomas, and DCC expression is undetectable in 90% of colon carcinoma cell lines. One DCC allele is also deleted in 50% of human colon adenomas, but results from protein expression studies have differed as to whether complete loss of DCC expression could occur in colon adenomas, or instead correlates with progression of colon adenoma to carcinoma. To further examine the timing of DCC expression loss in colon adenomas, we assayed DCC transcript levels in adenoma cell lines and tissues. We measured DCC expression by a sensitive assay using Southern blot detection of the RT-PCR-amplified DCC transcript. DCC expression was negligible or greatly reduced in 4 of 14 colon adenomas, including 2 of 2 adenoma cell lines and 2 of 12 adenoma tissue samples. These data are the first evidence that expression of DCC transcript can be silenced in colon adenoma cell lines and tissues. These data indicate that loss of DCC expression occurs in some colon adenomas, but is insufficient to drive the adenoma to carcinoma progression.