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Sporadic Amplification of the HER2/neu Protooncogene in Adenocarcinomas of Various Tissues¹

The Department of Chemical Immunology, The Weizmann Institute of Science, Rehovot [M. T., M. W., Z. J., R. K., D. G., J. S.]; Belinson Medical Center, Petah Tikva [A. D.]; and Tel-Aviv University Medical School, Tel-Aviv [M. G., D. A.], Israel

The HER2/neu protooncogene was found to be amplified in 6 of 109 primary adenocarcinoma tumors. No HER2/neu amplification was found in 29 other primary nonadenocarcinomatous tumors. In two colon tumors, in addition to the amplification, DNA rearrangement of HER2/neu gene was also observed. The rearrangement was explored in detail in one tumor and it was shown to be confined to the 3' region of the gene. Moreover, this tumor expressed an aberrant HER2/neu polypeptide with a molecular weight of 190,000, which is larger by approximately 5,000 than the molecular weight of the normal HER2/neu protein. The aberrant HER2/neu protein was immunoprecipitated with site-specific antibodies against a synthetic peptide from the COOH-terminal end of the normal HER2/neu protein; it also displayed intrinsic protein tyrosine kinase activity leading to self-phosphorylation.

¹ This work was supported by a grant from the NIH (CA25820) and by a grant from the US/Israel Binational Science Foundation (J. S.).

² To whom requests for reprints should be addressed, at Rorer Biotechnology, Inc., 4 Research Court, Rockville, MD 20850.

Received 9/ 8/87. Revised 12/ 4/87. Accepted 12/11/87.

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