A VERY LARGE VILLOUS ADENOMA WITH AN ADJACENT CANCER OF THE RECTUM - AN INFORMATIVE CASE FOR TESTING THE PROPOSED MOLECULAR-BASIS OF COLORECTAL TUMORIGENESIS

It is currently accepted that colorectal tumorigenesis results from ac cumulation of multiple mutations in certain genes. This concept prompt ed us to search for possible mutations in the APC, k-ras, and p53 gene s in an advanced cancer coexisting with a large villous adenoma of the rectum in a 54-year-old patient with no family history of colorectal cancer. Genomic DNA extracted from multiple subregions of the tumor an d surrounding normal mucosa was studied by polymerase chain reaction ( PCR) followed by single-strand conformation polymorphism (SSCP) analys is and direct sequencing. Both the adenoma and carcinoma had abnormal PCR-SSCP for APC (exon II) and k-ras, irrespective of the location wit hin the tumors. However, p53 abnormality (exon 7) was detected only in samples taken from the carcinoma. Subsequent sequencing revealed a TT G to TAC mutation at codon 479 of APC, a GGT to CAT mutation at codon 12 of k-ras in both the adenoma and carcinoma, and a CGG to TGG mutati on at codon 248 of p53 (exon 7) in the carcinoma. These findings were in accord with the current concept of colorectal tumor progression whe reby genetic alteration of APC and k-ras occurs relatively early while that of p53 is rather late and is possibly a decisive event in relati on to malignancy.