Landscaping the Cancer Terrain

Abstract

Few lines of investigation have taught us more about cancer than the study of inherited tumor susceptibility syndromes. Initially, the mutations responsible for these diseases were thought to promote malignancy in a straightforward manner, through inactivation of “tumor suppressor” genes, which directly modulate cell birth or cell death. More recently, however, susceptibility genes that work through less-direct mechanisms have come to light. The genes defective in patients with juvenile polyposis syndromes (JPSs), for example—one of which is described on page 1086 of this issue (1)—illuminate this principle and also raise fundamental questions about the relation between neoplastic cells and the “other cells” that together constitute a tumor mass.