A Matter of Dosage

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Science  25 Oct 2002:
Vol. 298, Issue 5594, pp. 761-763
DOI: 10.1126/science.1077707

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The canonical hypothesis of tumorigenesis is Knudson's two-hit model, which stipulates that both alleles of a tumor suppressor gene must be inactivated for tumors to form. In their Perspective, Fodde and Smits discuss new work revealing that this model may not hold for a subgroup of tumor suppressor genes. Inactivation of only one allele of these tumor suppressor genes is sufficient, either on its own or in combination with other deleterious events, to cause tumor formation.