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Incidence of Activating ras Oncogene Mutations Associated with Primary and Metastatic Human Breast Cancer¹

Cancer Research Institute, University of California at San Francisco, San Francisco, California 94143 [C. F. R., G. K. S., J. M. D., E. L., C. C. B.], and Peralta Cancer Research Institute, Oakland, California 94609 [C. D., H. S. S.]

To test the hypothesis that ras activation is involved in the final stages of breast cancer progression, we analyzed tumor DNA derived from 60 different patients and extracted from 40 invasive primary breast tumors, seven lymph node and skin metastases, nine metastatic effusions, and five established breast cancer cell lines. The polymerase chain reaction technique was used to amplify DNA fragments containing Kirsten-(Ki-), Harvey-(Ha-), and N-ras codons 12, 13, and 61 which were then probed on slot-blots with labeled synthetic oligomers to detect nonconservative single base mutations. Activating mutations were found in one of 40 primary tumors (Ki-ras codon 13), zero of seven lymph node and skin metastases, one of nine metastatic effusions (Ki-ras codon 12), and two of five cell lines (Ki-ras codons 12 and 13). These results indicate that activating ras mutations are rarely involved in either the initiation or metastatic progression of human breast cancer.

¹ This work was supported in part by Grants CA-44768 and CA-36773 from the National Cancer Institute and CH-235 from the American Cancer Society.

² Recipient of support from a grant from the German Volkswagon Stiftung, Hanover, West Germany. Present address: Free University of Berlin, Berlin, West Germany.

³ Present address: Lineberger Cancer Research Center, Chapel Hill, NC 27599.

⁴ To whom requests for reprints should be addressed.

Received 7/18/88. Revised 10/14/88. Accepted 10/20/88.

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