Cumulative Haploinsufficiency and Triplosensitivity Drive Aneuploidy Patterns to Shape the Cancer Genome
By T. Davoli, A. W. Xu, Kristen E. Mengwasser, Laura M. Sack, John C. Yoon, P. Park, Stephen J. Elledge. Cell, 2013
779 citations recorded by the source corpus.
Summary Aneuploidy has been recognized as a hallmark of cancer for over 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 >8200 tumor-normal pairs we provide statistical evidence suggesting 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 the 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.
Subfields: Cancer Research, Genetics, Plant Science
View Paper: https://www.semanticscholar.org/paper/d2d3964f8c3b0501ab145488c1eb77bd0434b402
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Citations in the corpus
- Evaluating the evaluation of cancer driver genes (2016, neutral): “Other ratiometric approaches use mutation functional impact bias (7), mutational clustering patterns (8, 9), or mutation composition patterns (9).”
- The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4 (2015, background): “Ectopic expression ofGATA3—another GATA familymemberpredicted tobea strong tumor suppressor (47, 48)—did not increase expression of genes associated with the SASP.”