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Allelic Loss and Mutational Analysis of the DPC4 Gene in Esophageal Adenocarcinoma¹

Program in Cancer Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104 [M. T. B., B. J. R.]; Departments of Medicine and Genetics, University of Washington, Seattle, Washington 98195 [B. J. R.]; and Department of Pathology, The Johns Hopkins Medical Institution, Baltimore Maryland 21205-2196 [M. S., S. E. K.]

DPC4, a recently cloned gene located on 18q21.1, is inactivated in almost one half of pancreatic adenocarcinomas. To determine whether DPC4 inactivation is involved in esophageal adenocarcinoma, we have analyzed aneuploid populations from biopsies of 35 patients with Barrett's esophagus who had premalignant epithelium, adenocarcinoma, or both. Sixteen of 35 patients (46%) had allelic loss at 18q21.1, including 7 patients who had only premalignant tissue present in their Barrett segment. In addition, three of four patients (75%) with 18q21.1 loss in their aneuploid populations had the allelic loss present in diploid cells. Mutational analysis of DPC4 did not reveal any inactivating alterations in the gene. These data indicate that allelic losses at 18q are selected during neoplastic progression in Barrett's esophagus, but the targeted gene remains to be identified.

¹ This work was supported by NIH Grant RO1 CA61202-02 and American Cancer Society Grant EDT-80683.

² To whom requests for reprints should be addressed, at Program in Cancer Biology, Fred Hutchinson Cancer Research Center, 1124 Columbia Street, Seattle. WA 98104.

Received 7/ 9/96. Accepted 8/16/96.

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