Quantifying Clonal and Subclonal Passenger Mutations in Cancer Evolution.
The vast majority of mutations in the exome of cancer cells are passengers, which do not affect the reproductive rate of the cell. Passengers can provide important information about the evolutionary history of an individual cancer, and serve as a molecular clock. Passengers can also become targets f...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-02-01
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| Series: | PLoS Computational Biology |
| Online Access: | http://europepmc.org/articles/PMC4734774?pdf=render |
| _version_ | 1824006504547614720 |
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| author | Ivana Bozic Jeffrey M Gerold Martin A Nowak |
| author_facet | Ivana Bozic Jeffrey M Gerold Martin A Nowak |
| author_sort | Ivana Bozic |
| collection | DOAJ |
| description | The vast majority of mutations in the exome of cancer cells are passengers, which do not affect the reproductive rate of the cell. Passengers can provide important information about the evolutionary history of an individual cancer, and serve as a molecular clock. Passengers can also become targets for immunotherapy or confer resistance to treatment. We study the stochastic expansion of a population of cancer cells describing the growth of primary tumors or metastatic lesions. We first analyze the process by looking forward in time and calculate the fixation probabilities and frequencies of successive passenger mutations ordered by their time of appearance. We compute the likelihood of specific evolutionary trees, thereby informing the phylogenetic reconstruction of cancer evolution in individual patients. Next, we derive results looking backward in time: for a given subclonal mutation we estimate the number of cancer cells that were present at the time when that mutation arose. We derive exact formulas for the expected numbers of subclonal mutations of any frequency. Fitting this formula to cancer sequencing data leads to an estimate for the ratio of birth and death rates of cancer cells during the early stages of clonal expansion. |
| first_indexed | 2024-12-18T20:28:15Z |
| format | Article |
| id | doaj.art-b8bc7d19abea437b9e87f7450fdbeaff |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-18T20:28:15Z |
| publishDate | 2016-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-b8bc7d19abea437b9e87f7450fdbeaff2022-12-21T20:54:09ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582016-02-01122e100473110.1371/journal.pcbi.1004731Quantifying Clonal and Subclonal Passenger Mutations in Cancer Evolution.Ivana BozicJeffrey M GeroldMartin A NowakThe vast majority of mutations in the exome of cancer cells are passengers, which do not affect the reproductive rate of the cell. Passengers can provide important information about the evolutionary history of an individual cancer, and serve as a molecular clock. Passengers can also become targets for immunotherapy or confer resistance to treatment. We study the stochastic expansion of a population of cancer cells describing the growth of primary tumors or metastatic lesions. We first analyze the process by looking forward in time and calculate the fixation probabilities and frequencies of successive passenger mutations ordered by their time of appearance. We compute the likelihood of specific evolutionary trees, thereby informing the phylogenetic reconstruction of cancer evolution in individual patients. Next, we derive results looking backward in time: for a given subclonal mutation we estimate the number of cancer cells that were present at the time when that mutation arose. We derive exact formulas for the expected numbers of subclonal mutations of any frequency. Fitting this formula to cancer sequencing data leads to an estimate for the ratio of birth and death rates of cancer cells during the early stages of clonal expansion.http://europepmc.org/articles/PMC4734774?pdf=render |
| spellingShingle | Ivana Bozic Jeffrey M Gerold Martin A Nowak Quantifying Clonal and Subclonal Passenger Mutations in Cancer Evolution. PLoS Computational Biology |
| title | Quantifying Clonal and Subclonal Passenger Mutations in Cancer Evolution. |
| title_full | Quantifying Clonal and Subclonal Passenger Mutations in Cancer Evolution. |
| title_fullStr | Quantifying Clonal and Subclonal Passenger Mutations in Cancer Evolution. |
| title_full_unstemmed | Quantifying Clonal and Subclonal Passenger Mutations in Cancer Evolution. |
| title_short | Quantifying Clonal and Subclonal Passenger Mutations in Cancer Evolution. |
| title_sort | quantifying clonal and subclonal passenger mutations in cancer evolution |
| url | http://europepmc.org/articles/PMC4734774?pdf=render |
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