When is precancerous actually postcancerous?

Demonstration that certain rare cancer-related mutations can (i) be shared by adjoining benign and cancerous tumor regions or (ii) be present solely i n a cancerous but not in an adjoining benign tumor region are data often ci ted in strong supportof the conventional idea that benign tumor regions con sist of precancerous cells. However, considering the well-documented eviden ce that many malignant cell types are still capable of regression through d ifferentiation, one can envisage an alternative (or coincident) scenario wh ereby (i) mutations are shared by adjoining benign and cancerous tumor regi ons because a cancer cell with a non-differentiation;impairing mutation dif ferentiates into a benign (postcancerous) cell or (ii) mutations are presen t solely in a cancerous tumor region because a cancer cell acquires a diffe rentiation-impairing mutation that prevents its regression into a benign ce ll. Only with higher-resolution lineage analyses of a type not yet performe d but experimentally feasible can these scenarios be distinguished. Accordi ngly, it is quite possible that common cancers regularly differentiate, suc h that a benign tumor region may actually harbor not only precancerous but also postcancerous cells. Demonstration of this phenomenon and elucidation of its mechanism could lead to novel therapeutics designed to effect revers ion of the more common cancers that, when in advanced stages, are notorious ly inadequately treated by current cytotoxic regimens. (C) 2000 Wiley-Liss, Inc.