Universal Patterns of Selection in Cancer and Somatic Tissues
By Iñigo Martincorena, K. Raine, Moritz Gerstung, Kevin J. Dawson, Kerstin Haase, P. van Loo, Helen R. Davies, Michael R. Stratton, Peter J. Campbell. Cell, 2018
854 citations recorded by the source corpus.
Cancer develops as a result of somatic mutation and clonal selection, but quantitative measures of selection in cancer evolution are lacking. We applied methods from evolutionary genomics to 7,664 human cancers across 29 tumor types. Unlike species evolution, positive selection outweighs negative selection during cancer development. On average, <1 coding base substitution/tumor is lost through negative selection, with purifying selection only detected for truncating mutations in essential genes in haploid regions. This allows exome-wide enumeration of all driver mutations, including outside known cancer genes. On average, tumors carry ~4 coding substitutions under positive selection, ranging from <1/tumor in thyroid and testicular cancers to >10/tumor in endometrial and colorectal cancers. Half of driver substitutions occur in yet-to-be-discovered cancer genes. With increasing mutation burden, numbers of driver mutations increase, but not linearly. We identify novel cancer genes and show that genes vary extensively in what proportion of mutations are drivers versus passengers.
Subfields: Cancer Research, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/f39a501ef1c24625592530177e8bb6eea7b18d7d
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Citations in the corpus
- Intratumoral heterogeneity in cancer progression and response to immunotherapy (2021, positive): “On the contrary, passenger mutations (which do not offer selective advantages) evolve neutrally{Martincorena, 2017, 29056346}, and their branched evolution is considered the main source of clonal diversity in established tumors.”