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| Microsatellite instability-associated mutations associate preferentially with the intestinal type of primary gastric carcinomas in a high-risk population |
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| Author(s): Chung YJ, Song JM, Lee JY, Jung YT, Seo EJ, Choi SW, Rhyu MG |
| Source: CANCER RESEARCH Volume: 56 Issue: 20 Pages: 4662-4665 Published: OCT 15 1996 |
| Times Cited: 85 References: 25 |
| Abstract: Most colon cancers exhibiting microsatellite instability (MI), a mutator phenotype of mismatch repair failure, are associated with mutations of the transforming growth factor-beta receptor type II genes (TGF-beta RII). Of intestinal- and diffuse-type gastric carcinomas, the former have been thought to arise from intestinal metaplasia in which gastric mucosa resembles intestinal mucosa. To evaluate the preferential histological type of RII-associated mutations in the development of gastric carcinoma, mutations of TGF-beta RII, p53, and p16 were analyzed for the two types of primary gastric carcinomas showing MI. Of 50 primary gastric carcinomas, including 33 intestinal types and 17 diffuse types, 15 cases (30%) demonstrated MI at 1 or more of the 11 mitrosatellite markers tested. The 15 MI cases were classified into two groups, widespread MI and low-level MI, based on the number of markers exhibiting the instability, Eleven mere widespread MIs, and the remaining four cases were low-level MIs. Ten of the 11 (91%) widespread MIs were of the intestinal type, and 1 case (9%) was of the diffuse type. Of the 11 widespread MIs, 10 cases (91%) demonstrated frameshift mutations within the polyadenylate tract of the TGF-beta RII. The frameshift mutation was rarety detected at p53 and p16 (1 of 11, 9%). In contrast, the four low-level MI cases had no frameshift mutations within the repeat sequences of TGF-beta RII, p53, and p16, but two of the four cases demonstrated base substitution mutations within p53. Our results suggest that mismatch repair failure call mutate the TGF-beta RII and may provide one of the pathways for the development of the intestinal-type gastric carcinoma in high-risk populations. |
| Document Type: Article |
| Language: English |
Addresses:
1. CATHOLIC UNIV MED COLL, DEPT MICROBIOL, SEOUL 137701, SOUTH KOREA
2. CATHOLIC UNIV MED COLL, ST PAULS HOSP, DEPT CLIN PATHOL, SEOUL 137701, SOUTH KOREA
3. CATHOLIC UNIV MED COLL, ST PAULS HOSP, DEPT INTERNAL MED, SEOUL 137701, SOUTH KOREA |
| Publisher: AMER ASSOC CANCER RESEARCH, PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 |
| Subject Category: Oncology |
| IDS Number: VL756 |
| ISSN: 0008-5472 |
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