2024-03-28T20:16:04Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/2187382021-12-28T15:41:22Zcom_10261_9676com_10261_8col_10261_9677
00925njm 22002777a 4500
dc
Heredia-Genestar, José María
author
Marqués-Bonet, Tomàs
author
Juan, David
author
Navarro, Arcadi
author
2020-05-19
Mutations do not accumulate uniformly across the genome. Human germline and tumor mutation density correlate poorly, and each is associated with different genomic features. Here, we use non-human great ape (NHGA) germlines to determine human germline- and tumor-specific deviations from an ancestral-like great ape genome-wide mutational landscape. Strikingly, we find that the distribution of mutation densities in tumors presents a stronger correlation with NHGA than with human germlines. This effect is driven by human-specific differences in the distribution of mutations at non-CpG sites. We propose that ancestral human demographic events, together with the human-specific mutation slowdown, disrupted the human genome-wide distribution of mutation densities. Tumors partially recover this distribution by accumulating preneoplastic-like somatic mutations. Our results highlight the potential utility of using NHGA population data, rather than human controls, to establish the expected mutational background of healthy somatic cells.
Nature Communications 11: 2512 (2020)
http://hdl.handle.net/10261/218738
10.1038/s41467-020-16296-4
2041-1723
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/501100000780
http://dx.doi.org/10.13039/501100002809
http://dx.doi.org/10.13039/100000011
http://dx.doi.org/10.13039/501100004587
http://dx.doi.org/10.13039/501100011033
32427823
Extreme differences between human germline and tumor mutation densities are driven by ancestral human-specific deviations