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Evidence for Lack of Enhanced Hedgehog Target Gene Expression in Common Extracutaneous Tumors¹

The Cooperative Human Tissue Network, University of Alabama, Birmingham, AL 35294 [G. A.]; Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland 20892 [L. K.]; Departments of Dermatology [Z. H., J. M. B., M. A., E. H. E.]; and Neurological Surgery [Y. L., S. O.]; San Francisco General Hospital and the University of California School of Medicine, San Francisco, California 94110; Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756 [M. A. I.]; and Department of Dermatology, Columbia University, New York, New York 10032 [D. R. B.]

Abnormal hedgehog signaling, most commonly caused by loss of PTCH1 inhibitor activity,drives tumorigenesis of basal cell carcinomas (BCCs). To assess whether other tumors also have abnormal hedgehog signaling, we have assayed RNA from common cancers at nine different sites for levels of expression of hedgehog target genes that are up-regulated uniformly in BCCs. We report here that such dysregulation appears not to be common in the types of non-BCC cancers studied, indicating that the molecular pathogenesis of BCCs, like their frequency and behavior, differs markedly from that of most other cancers.

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