ALLELIC DELETIONS OF MCC/APC AND P53 ARE FREQUENT LATE EVENTS IN HUMAN GASTRIC CARCINOGENESIS

Background/Aims: Frequent allelic deletion affecting the mutated in colon cancer/adenomatous polyposis coli (MCC/APC) and p53 tumor suppressor gene loci has been reported in human cancers. However, simultaneous correlative analyses of these two abnormalities or their timing in gastric tumorigenesis have not been performed. Methods: To ascertain the relation between and timing of allelic deletions of MCC/APC and p53 in gastric carcinogenesis, 52 matched sets of normal tissue, gastric carcinoma, and adjacent gastric dysplasia were evaluated. Results: Allelic deletion was seen in 33% of informative cancers at MCC, in 34% at APC, and in 64% at p53. Losses involving MCC correlated exactly with those affecting APC. Limited mutational analysis failed to reveal point mutations in selected exons of MCC. The frequencies of allelic losses at the two loci did not differ significantly among histological types. There was no allelic loss in gastric dysplasia. Interestingly, allelic deletion at MCC/APC was never detected in tumors negative for allelic deletion of p53. Conclusions: These results suggest that allelic deletions involving p53 and MCC/APC are common late events in gastric cancer. They also imply that allelic deletions affecting MCC/APC may not occur independently of those involving p53 in gastric tumorigenesis. © 1994.