First, proto-oncogenes need to be activated through mutations, and mutations are rare events. Second, tumor suppressor genes need to be inactivated, but typically two copies exist of each tumor suppressor gene, and thus two independent mutations are needed to inactivate a tumor suppressor, an even rarer event. Vogelstein provided the third answer. Activating or inactivating any single gene, he postulated, produced only the first steps toward carcinogenesis. Cancer’s march was long and slow and proceeded though many mutations in many genes over many iterations. In genetic terms, our cells were
...more
