Stem cell regulation, tissue ontogeny, and oncogenic events.

The number of necessary oncogenic events is a function of tissue ontogeny. A minimum of two events appears to suffice for certain embryonal tumors, leukemias, and lymphomas for which the target tissues normally show stem cell proliferation. Other tumors, including those featured in the Li-Fraumeni syndrome, arise in target tissues whose stem cells are conditionally stimulated to proliferate, as in response to hormones, and involve more events. The most complex cancers include most carcinomas, which arise in renewal tissues whose stem cells do not normally proliferate. The number of necessary oncogenic events appears to increase with the number of controls on proliferation.