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Alterations of (CA)_n DNA Repeats and Tumor Suppressor Genes in Human Gastric Cancer¹

Unit of Multistage Carcinogenesis, International Agency for Research on Cancer, Lyon, France [N. M., A-M. A., Y. O., H. Y], and Laboratory of Tumour Biochemistry [G. I. P.] and Abdominal Department of the Cancer Research Center, [0. V. G., A. A. K.], Moscow, Russia

² To whom requests for reprints should be addressed, at International Agency for Research on Cancer, 150, cours Albert Thomas, 69372 Lyon cedex 08, France.

We have examined whether alterations of simple (CA)_n DNA repeats, as observed in human colon cancers, occur during human gastric carcinogenesis and whether such alterations reflect genomic instability that could lead to other genetic changes. A total of 22 gastric cancer samples were analyzed: 15 well or moderately differentiated adenocarcinomas, 6 signetring cell carcinomas, and 1 poorly differentiated adenocarcinoma. When (CA)_n repeat sequences were examined at 10 loci, one adenocarcinoma showed a loss of repeat sequences at five loci, three adenocarcinomas gained a repeat at one locus, and one adenocarcinoma had new, repeated sequences at five loci. Three samples showed mutations in the p53 gene, two in exon 5 (both GC to AT transition at a CpG dinucleotide) and one in exon 7 (AT to GC transition). Only one sample with a p53 mutation also showed altered (CA)_n repeats. A putative tumor suppressor gene, connexin 32, was not altered as assessed by single-strand conformation polymorphism analysis. These results suggest that genomic instability revealed by (CA)_n repeat changes does not seem to contribute to induction of point mutations in p53 or connexin 32 genes but may participate in loss of heterozygosity at APC/MCC loci. The results are consistent with the hypothesis that different mechanisms are involved in the gain and loss of (CA)_n repeats.

¹ This work was partly supported by NIH Grant RO1-CA-40534. Y. O. was a recipient of a Research Training Fellowship awarded by the International Agency for Research on Cancer.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 10/20/93. Accepted 11/19/93.

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