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Ubiquitous Somatic Alterations at Microsatellite Alleles Occur Infrequently in Barrett's-associated Esophageal Adenocarcinoma¹

Department of Medical Genetics, The Queen's University of Belfast, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, Northern Ireland [C. M. G., S. E. H. R.]; Department of Pathology [J. M. S.] and The Regional Thoracic Unit [J. A. M., A. J. R.], Royal Victoria Hospital, Grosvenor Road, Belfast BT12 6BJ, Northern Ireland; and Marshfield Medical Research Foundation, Marshfield, Wisconsin 54449-5790 [J. L. W.]

Microsatellite alterations have been documented in a subset of sporadic tumors, including those of the colon, lung, bladder, stomach, and esophagus. This study documented the frequency of microsatellite alterations at 139 loci, comprising predominantly dinucleotide and tetranucleotide repeat units, in 17 cases of primary esophageal adenocarcinoma arising against a background of Barrett's metaphasia. Each tumor demonstrated alterations in at least one locus studied. Widespread microsatellite alterations, occurring at 45.3% (58 of 128) of loci tested, were detected in a single case. The remaining 16 tumors exhibited low levels of microsatellite instability, ranging from 0.8% (1 of 128) to 8.1% (10 of 123) of loci tested. The single case with ubiquitous somatic alterations showed no significant difference in the incidence of novel alleles at di- and tetranucleotide repeat loci. The 16 cases showing a low level of microsatellite alterations demonstrated a 3.3-fold higher incidence of novel alleles at tetranucleotide repeat loci compared to dinucleotide repeat loci. These data suggest that ubiquitous somatic alterations at microsatellite loci, considered a phenotypic expression of defective mismatch repair, occur infrequently in Barrett's-associated adenocarcinoma. However, the majority of these tumors demonstrate a low level of microsatellite alterations, perhaps reflecting the inherent instability of these markers.

¹ This work was supported by a grant from The Northern Ireland Chest, Heart and Stroke Association, and NIH Grant HG00835.

² To whom requests for reprints should be addressed. Phone: (01232) 329241, ext. 2221; Fax: (01232) 236911.

Received 9/ 6/95. Accepted 11/29/95.

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