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Amplification, Overexpression, and Rearrangement of the erbB-2 Protooncogene in Primary Human Stomach Carcinomas

Department of Biochemistry, College of Medicine, Seoul National University, Seoul 110-744 Korea [J-B. P., S-C. P., S-W. K.], and Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892 [J. S. R., M. H. K.]

Four of 51 primary gastric carcinomas exhibited amplification of the erbB-2 protooncogene ranging from 2- to 8-fold. In three cases gene amplification affected erbB-2 alleles of normal gene structure as determined by Southern blot analysis. In addition, one tumor displayed gene amplification of an apparently rearranged erbB-2 allele. Analysis of the rearranged allele revealed a structural alteration consistent with an internal deletion of approximately 2 kilobase pairs within the erbB-2 gene. Quantitation of erbB-2 mRNA in these tumors demonstrated that gene amplification coincided with overexpression of erbB-2 mRNA ranging from 8- to 32-fold above levels observed in stomach tumors without gene amplification. Furthermore, in one of the tumors with amplified normal size erbB-2 restriction fragments, elevated erbB-2 mRNA levels consisted of the normal size 5-kilobase transcript. Thus, overexpression of normal size erbB-2 mRNA accompanies gene amplification in primary stomach tumors. In addition, evidence for erbB-2 gene rearrangement suggests a role for such alteration in the development of certain gastric carcinomas.

¹ To whom requests for reprints should be addressed, at National Cancer Institute, Building 37, Room 1E24, Bethesda, MD 20892.

Received 3/16/89. Revised 8/16/89. Accepted 9/ 5/89.

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