The study investigates the role of the beclin 1 autophagy gene in tumor suppression. Beclin 1 is monoallelically deleted in a significant percentage of human cancers, suggesting it may be a tumor suppressor. Using a targeted mutant mouse model, the researchers found that heterozygous disruption of beclin 1 increases the frequency of spontaneous malignancies and accelerates the development of hepatitis B virus-induced premalignant lesions. Molecular analyses showed that the remaining wild-type allele is neither mutated nor silenced. Heterozygous disruption of beclin 1 results in increased cellular proliferation and reduced autophagy in vivo. These findings demonstrate that beclin 1 is a haplo-insufficient tumor-suppressor gene and provide genetic evidence that autophagy is a novel mechanism of cell-growth control and tumor suppression. The study suggests that mutation of beclin 1 or other autophagy genes may contribute to the pathogenesis of human cancers.The study investigates the role of the beclin 1 autophagy gene in tumor suppression. Beclin 1 is monoallelically deleted in a significant percentage of human cancers, suggesting it may be a tumor suppressor. Using a targeted mutant mouse model, the researchers found that heterozygous disruption of beclin 1 increases the frequency of spontaneous malignancies and accelerates the development of hepatitis B virus-induced premalignant lesions. Molecular analyses showed that the remaining wild-type allele is neither mutated nor silenced. Heterozygous disruption of beclin 1 results in increased cellular proliferation and reduced autophagy in vivo. These findings demonstrate that beclin 1 is a haplo-insufficient tumor-suppressor gene and provide genetic evidence that autophagy is a novel mechanism of cell-growth control and tumor suppression. The study suggests that mutation of beclin 1 or other autophagy genes may contribute to the pathogenesis of human cancers.