Evidence for a Common Molecular Pathogenesis in Colorectal, Gastric, and Pancreatic Cancer

Abstract

We examined tissue extracted from 19 gastric, 7 pancreatic, and 23 colorectal carcinoma specimens to determine the comparative incidence of allele loss on chromosomes 5, 17, and 18 and that of KRAS2 point mutations. Chromosome 5 allele loss occurred at the same frequency in all three gastrointestinal tumors (approximately 30%), whereas chromosome 17 and 18 allele losses were seen at a significantly lower frequency in gastric (20%) and pancreatic (0%) malignancies than in colorectal cancer (57%). Point mutations in KRAS2 were seen in 83% of pancreatic and 52% of colon cancers, but not in gastric cancer specimens. In pancreatic tumors, these mutations were always found in the second nucleotide of codon 12. In colorectal cancer, the distribution was more variable, involving the second nucleotide of codon 13 and both the first and second nucleotides of codon 12. These results suggest that inactivation of the adenomatous polyposis coli gene on chromosome 5 may be an initiating step for carcinomas of the stomach and pancreas as well as of the colon, but that the genes involved in tumor progression events may be tissue- or tumor-specific.

Allelotype analysis of adenocarcinoma of the gastric cardia

“…Third, the selection of tumour-rich regions for molecular analysis, may have facilitated a more reliable detection of AT than the study of DNA from unfractionated tumours, a factor that may have contributed to the detection of lower rates of allele loss in some studies (Wada et al, 1988 (Flejou et al, 1994). (Neuman et al, 1991;Sano et al, 1991;McKie et al, 1993;Ranzani et al, 1993;Rhyu et al, 1994). However, loss of the APC/MCC gene loci on 5q was documented in over 80% of flow-sorted, aneuploid cell populations in gastric carcinoma, suggesting that Sq LOH may be associated with the development of aneuploidy in these tumours (Tamura et al, 1993).…”

Three independent genetic profiles based on mucin expression in early differentiated-type gastric cancers—a new concept of genetic carcinogenesis of early differentiated-type adenocarcinomas

“…Others have reported that 5q allelic loss is found frequently in gastric adenomas. 29 This finding suggests that 5q allelic loss may be an initial genetic event in gastric tumorigenesis. Vogelstein et al have reported that LOH on chromosome 5q is frequently associated with colorectal adenomas and adenocarcinomas (most of which are well-differentiated adenocarcinomas).…”

Cellular markers in the gastric precancerous process

“…Others have reported a loss of heterozygosity at 18q in 20%, 101 and in 58% of gastric cancers, 93 but much less commonly in gastric adenomas. 93 As for APC, there are no studies describing DCC mutations or loss of heterozygosity at 18q at earlier stages of the gastric cancer process.…”