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A phylogenetic approach to study the evolution of somatic mutational processes in cancer
Vu, Tracy Choi, Jiyeong Townsend, Jeffrey P. Karim, Sajjad
Vu, Tracy
Choi, Jiyeong
Townsend, Jeffrey P.
Karim, Sajjad
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Journal article
Date
2022-06-22
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Biology
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http://dx.doi.org/10.1038/s42003-022-03560-0
Abstract
Cancer cell genomes change continuously due to mutations, and mutational processes change over time in patients, leaving dynamic signatures in the accumulated genomic variation in tumors. Many computational methods detect the relative activities of known mutation signatures. However, these methods may produce erroneous signatures when applied to individual branches in cancer cell phylogenies. Here, we show that the inference of branch-specific mutational signatures can be improved through a joint analysis of the collections of mutations mapped on proximal branches of the cancer cell phylogeny. This approach reduces the false-positive discovery rate of branch-specific signatures and can sometimes detect faint signatures. An analysis of empirical data from 61 lung cancer patients supports trends based on computer-simulated datasets for which the correct signatures are known. In lung cancer somatic variation, we detect a decreasing trend of smoking-related mutational processes over time and an increasing influence of APOBEC mutational processes as the tumor evolution progresses. These analyses also reveal patterns of conservation and divergence of mutational processes in cell lineages within patients.
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Miura, S., Vu, T., Choi, J. et al. A phylogenetic approach to study the evolution of somatic mutational processes in cancer. Commun Biol 5, 617 (2022). https://doi.org/10.1038/s42003-022-03560-0
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Nature Research
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Communications Biology, Vol. 5
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