Cumulative Haploinsufficiency and Triplosensitivity Drive Aneuploidy Patterns and Shape the Cancer Genome
| Autor: | John C. Yoon, Laura M. Sack, Kristen E. Mengwasser, Andrew Wei Xu, Teresa Davoli, Stephen J. Elledge, Peter J. Park |
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| Rok vydání: | 2013 |
| Předmět: |
Gene Dosage
Aneuploidy Biology Gene dosage Genome Article General Biochemistry Genetics and Molecular Biology law.invention 03 medical and health sciences 0302 clinical medicine law Neoplasms medicine Humans Genes Tumor Suppressor Copy-number variation Gene 030304 developmental biology Genetics 0303 health sciences Oncogene Biochemistry Genetics and Molecular Biology(all) Oncogenes medicine.disease 3. Good health 030220 oncology & carcinogenesis Suppressor Haploinsufficiency Algorithms |
| Zdroj: | Cell. 155:948-962 |
| ISSN: | 0092-8674 |
| Popis: | SummaryAneuploidy has been recognized as a hallmark of cancer for more than 100 years, yet no general theory to explain the recurring patterns of aneuploidy in cancer has emerged. Here, we develop Tumor Suppressor and Oncogene (TUSON) Explorer, a computational method that analyzes the patterns of mutational signatures in tumors and predicts the likelihood that any individual gene functions as a tumor suppressor (TSG) or oncogene (OG). By analyzing >8,200 tumor-normal pairs, we provide statistical evidence suggesting that many more genes possess cancer driver properties than anticipated, forming a continuum of oncogenic potential. Integrating our driver predictions with information on somatic copy number alterations, we find that the distribution and potency of TSGs (STOP genes), OGs, and essential genes (GO genes) on chromosomes can predict the complex patterns of aneuploidy and copy number variation characteristic of cancer genomes. We propose that the cancer genome is shaped through a process of cumulative haploinsufficiency and triplosensitivity. |
| Databáze: | OpenAIRE |
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