Recurrent Hemizygous Deletions in Cancers May Optimize Proliferative Potential

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Science  24 May 2012:
DOI: 10.1126/science.1219580

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Tumors exhibit numerous recurrent hemizygous focal deletions that contain no known tumor suppressors and are poorly understood. To investigate whether these regions contribute to tumorigenesis, we searched genetically for genes with cancer-relevant properties within these hemizygous deletions. We identified STOP and GO genes, which negatively and positively regulate proliferation, respectively. STOP genes include many known tumor suppressors, while GO genes are enriched for essential genes. Analysis of their chromosomal distribution revealed that recurring deletions preferentially over-represent STOP genes and under-represent GO genes. We propose a hypothesis called the Cancer Gene Island model whereby gene islands encompassing high densities of STOP genes and low densities of GO genes are hemizygously deleted to maximize proliferative fitness through cumulative haploinsufficiencies. Since thousands of genes are hemizygously deleted per tumor, this mechanism may help drive tumorigenesis.

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