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Science 15 May 1998:
Vol. 280. no. 5366, pp. 1036 - 1037
DOI: 10.1126/science.280.5366.1036
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Research Commentaries

ONCOGENESIS:
Landscaping the Cancer Terrain

Kenneth W. Kinzler and Bert Vogelstein

Colorectal cancer can arise as a result of spontaneous genetic lesions or an inherited defect. In this issue, Howe et al. report that the gene defective in one of the inherited syndromes is SMAD4, a member of a key signal transduction pathway. In their commentary, Kinzler and Vogelstein add this gene to a classification scheme for colorectal cancers that groups the offending genes as "gatekeepers," "caretakers," or "landscapers." Landscaping genes such as SMAD4 have an indirect effect on the tissue that will eventually become cancerous and create an abnormal microenvironment for the cells, probably by acting in the adjacent stromal cells.

The authors are in the Molecular Genetics Laboratory of the Johns Hopkins Oncology Center, Baltimore, MD 21231, USA.

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