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Fig. 2 | Clinical Epigenetics

Fig. 2

From: Cancer: evolutionary, genetic and epigenetic aspects

Fig. 2

Mutation-driven cancer differentiation. Tissue-specific transformation resistance of cell (TRC) values are determined, in part, by different numbers of rate-limiting events (mutations, indicated by lightning arrows) required for cancer appearance (denoted with © symbol). Tissues characterized by a low risk of cancer (low mass, low proliferation) are characterized by a low number of rate-limiting events and, consequently, by relatively big “differentiation leaps” shown as differently colored arrows (tissues (a) and (b)). On the contrary, the high risk of tissues with a large mass and active proliferation is offset by a greater number of mutations and a relatively smaller impact of each of them to differentiation (tissues (d) and (e)). A The TRC values of different tissues have been adjusted during evolution so that sporadic cancers arise mainly in the post-reproductive period of life (or do not arise at all). B A germ-line mutation in specific gene (red color) reduces the TRC value of all cells in the body, but to a different degree: to a greater degree in tissues (a) and (b), and to a lesser degree in tissues (d) and (e). In tissue (c), the “red” gene is not involved in carcinogenesis and its mutation is not manifested. As a result, there is a high probability of multiple tumors in individuals of reproductive age, and the spectra of these tumors may differ from those observed for sporadic tumors with the same genetic defect. Germ line mutations of cancer genes are thus subject to the purifying selection. (Reprinted from AV Lichtenstein (2008) Cancer: shift of the paradigm, Med Hypotheses 71(6):839–850, with permission from Elsevier)

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