The effect of tissue-specific growth patterns of target stem cells on the spectrum of tumours resulting from multistage tumorigenesis

A multistage mathematical model of tumorigenesis has been developed to expl ore the effects of target cell growth pattern on the proportions of turnour s deriving from different tissues (the tumour spectrum). Analytical modelli ng techniques have shown that the effect of the target cell growth pattern on the tumour spectrum also depends on the number of stages (gene mutations ) necessary for malignant change in cells of each tissue type. This suggest s the existence of temporal "windows of opportunity" for turnours of differ ent types in relation to stage number and growth kinetics. Models of this k ind are applicable to cancer-prone transgenic (e.g. p53 deficient) mice, wh ere homozygotes and heterozygotes differ in one carcinogenic stage, and dif fer also in the spectrum of tumours observed. Generally, turnours deriving from target stem cells which are developmentally short-lived will arise mor e frequently in homozygotes than heterozygotes. Such models may also be app licable to human syndromes (e.g. Li-Fraumeni) in which susceptibility to ca ncer is inherited. (C) 2001 Academic Press.