Somatic mutation of the APC gene in gastric cancer: frequent mutations in very well differentiated adenocarcinoma and signet-ring cell carcinoma

Abstract

We searched for somatic mutations of the adenomatous polyposis coli (APC) gene in DNA samples isolated from 57 sporadic gastric cancers, by means of a ribonuclease (RNase) protection analysis coupled with DNA amplification by the polymerase chain reaction (PCR). Examining 30% of the APC coding region, including a region where somatic mutations in colorectal tumors are known to be clustered, we detected somatic mutations in 12 tumors; seven in 17 very well differentiated adenocarcinomas, two in 19 well or moderately differentiated adenocarcinomas, and three in ten signet-ring cell carcinomas. So far, no somatic mutations have been identified in 11 poorly differentiated adenocarcinomas. Eight of the 17 somatic mutations found in 12 tumors caused truncation of the gene product due to a nonsense mutation and a 1-, 2- or 5-bp deletion; nine others were point mutations that altered amino acids. Our results suggest that inactivation of APC plays a role in development of some gastric cancers, particularly very well differentiated adenocarcinomas and signet-ring cell carcinomas.

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

“…This was an intestinal-type tumour. Nakatsuru et al (1992) identified APC gene mutations in 12 of 57 (21%) gastric cancers by RNAase protection analysis. These were differentiated carcinomas (intestinal-type according to classification of Lauren) and signet-ring cell carcinomas.…”

“…APC mutations have been detected in 20-40% of gastric adenomas (Nakatsuru et al, 1993;Tamura et al, 1994), which are thought to be precursors of some differentiated types of gastric cancer. Nakatsuru et al (1992) divided differentiated-type carcinomas into 'very well-differentiated' and 'well-or moderately differentiated' types and found mutations were significantly more frequent in the very well-differentiated carcinoma.…”

“…The combination of these techniques has led to the detection of causative APC germline mutations in 66% of families studied (Wells et al, unpublished observations). Approximately half of the APC mutations detected in gastric carcinomas by Nakatsuru et al (1992) using RNAase protection analysis were missense mutations. The sensitivity of SSCP for the detection of single base substitutions has been reported to be greatest for molecules shorter than 200 bp (Sheffield et al, 1993).…”

Dysregulated expression of β-catenin marks early neoplastic change in Apc mutant mice, but not all lesions arising in Msh2 deficient mice

“…However, a more general role for APC mutations in neoplasia is suggested by the fact that FAP patients have an increased predisposition to tumours of the brain, thyroid and bone and also to focal proliferative lesions (`desmoid tumours') of the connective tissue. Mutated APC has also been reported in a range of sporadic tumours, including pancreatic and gastric tumours and the majority of adenomas and carcinomas of the colorectum Horii et al, 1992;Nakatsuru et al, 1992). Furthermore, loss of heterozygosity at 5q21 has been observed in sporadic tumours of the breast and oesophagus (Boynton et al, 1992;Thompson et al, 1993;Kashiwaba et al, 1994).…”

Germline mutations of the APC gene in two Japanese adenomatous polyposis patients

“…Somatic mutations of the APC gene have been reported in sporadic colorectal cancer (Miki et al, 1992;Miyoshi et aL, 1992a;Nagase and Nakamura, 1993;Nishisho et aL, 1991) and other digestive tumors (Horii et aL, 1992a, b;Nakatsuru et al, 1992). These results suggest that inactivation of the APC gene plays a significant role in FAP carcinogenesis.…”