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Activated ras Oncogenes in Human Thyroid Cancers¹

CRC Thyroid Tumor Biology Research Group, Department of Pathology, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, United Kingdom [N. R. L., E. S. M., F. S. W., E. D. W., D. W-T.]; Section of Cell and Molecular Biology, Chester Beatty Laboratories, Institute of Cancer Research, Fulham Road, London SW3 6JB, United Kingdom [C. J. F.]; and Leukemia Research Fund Preleukemia Unit, Department of Hematology, University of Wales College of Medicine, Health Park, Cardiff CF4 4XN, United Kingdom [D. H., R. A. P.]

Human thyroid epithelial (follicular) cells give rise to two malignant tumors—"follicular" carcinomas, which metastasize almost exclusively via the bloodstream, and "papillary" carcinomas, which metastasize predominantly via lymphatics (Williams, E. D. In: W. Duncan (ed.), Recent Results in Cancer Research: Thyroid Cancer, pp. 47–55. Berlin: Springer-Verlag, 1980). We have investigated whether this contrast in biological behavior might be associated with different patterns of oncogene activation. DNA transfection analysis of five follicular and ten papillary cancers indeed showed a statistically significant difference in the pattern of genes responsible, activated ras oncogenes being found in 80% of follicular tumors but only 20% of papillary tumors. In addition, in follicular cancers we have found activation of all three ras oncogenes (H-ras, K-ras, and N-ras), the first time that this has been demonstrated in a primary human tumor type (as opposed to cell lines). We suggest therefore that ras activation may be an important determinant of metastatic capability in these epithelial cancers.

¹ This work was supported by grants from the Cancer Research Campaign of Great Britain.

² To whom requests for reprints should be addressed.

Received 1/27/88. Revised 5/16/88. Accepted 5/20/88.

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