The sequential accumulation of genetic alterations characteristic of the colorectal adenoma–carcinoma sequence does not occur between gastric adenoma and adenocarcinoma

Abstract

We screened 30 gastric adenomas and 72 gastric adenocarcinomas for four genetic alterations (mutations of the K-ras, APC, and p53 genes and loss of heterozygosity at the DCC genetic locus) which are known to occur during colorectal tumourigenesis. We used polymerase chain reaction (PCR) single-strand conformation polymorphism analysis to detect mutations. Loss of heterozygosity (LOH) at the DCC locus was ascertained directly by performing PCR on the variable number of tandem repeats within the gene. Mutations of the K-ras gene were not detected in any gastric adenoma or carcinoma. APC mutations were detected in 20 per cent (6/30) of the adenomas but in only 1.4 per cent (1/72) of the carcinomas. In contrast, the p53 gene was frequently mutated in carcinomas (35 per cent; 25/72), but not in adenomas. LOH at the DCC locus was a frequent occurrence in carcinomas (58 per cent; 11/19 informative cases) but was infrequent in adenomas (14 per cent; 1/7). Alterations of the p53 and DCC genes occurred frequently both in differentiated and in undifferentiated gastric carcinomas. The considerable differences in the incidences of genetic alterations between gastric adenoma and carcinoma indicate that the sequential development of gastric carcinoma from adenoma is uncommon in gastric carcinogenesis.

Infrequent alterations of the APC and MCC genes in gastric cancers from British patients

“…However, no mutations were detected in 24 gastric carcinomas by Ogasawara et al (1994) using SSCP analysis. In a larger study, these authors later found APC to be mutated in only one of 72 (1.4%) gastric cancers, a signetring cell carcinoma (Maesawa et al, 1995). Considering these results it is probable that APC gene mutations do not occur in the majority of gastric cancers.…”

“…Furthermore, somatic mutations of the APC gene have been described in several tumour types such as pancreatic cancer , oral squamous-cell carcinoma (Uzawa et al, 1994) and oesophageal cancer (Powell et al, 1994). In the stomach, APC mutations have been reported in gastric adenomas (Nakatsuru et al, 1993;Tamura et al, 1994) and in differentiated and signet-ring cell carcinomas Maesawa et al, 1995). These studies have involved analysis of gastric tumours from Japanese patients.…”

Reduced expression of the insulin‐induced protein 1 and p41 Arp2/3 complex genes in human gastric cancers

“…1 As underlying genetic and epigenetic alterations, mutations of p53 have been reported in 35-56% of human gastric cancers, [2][3][4] and silencing of p16 by its promoter hypermethylation has been reported in 42.0 -42.2%. 5,6 Mutations of K-RAS and APC genes, however, are observed only at very low frequencies, in the ranges of 0 -3.6% and 0 -1.4%, respectively.…”

“…5,6 Mutations of K-RAS and APC genes, however, are observed only at very low frequencies, in the ranges of 0 -3.6% and 0 -1.4%, respectively. 3,7,8 As a factor that influences the accumulation of genetic alterations, microsatellite instability (MSI) is observed at high incidences, ranging from 31-67%. 9,10 MSI is rarely caused by mutations of DNA-mismatch-repair genes such as hMLH1 and hMSH2, 10,11 but hypermethylation of the hMLH1 promoter region is observed in gastric cancers with MSI.…”

Epigenetic alterations in gastric carcinogenesis

“…It has been demonstrated that some gastric carcinoma may arise from gastric adenomas or flat dysplasias, similar to the consequence of colorectal adenoma derived from adenocarcinoma [25][26][27][28]. The cumulative prevalence of malignant transformation of gastric dysplasia/adenoma has been reported to be greater than 10% in long-term follow-up studies [29,30].…”