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. 2014 Mar;42(5):2870-8.
doi: 10.1093/nar/gkt1320. Epub 2013 Dec 25.

A phylogenetic model for understanding the effect of gene duplication on cancer progression

Qin Ma  1 , Jaxk H Reeves, David A Liberles, Lili Yu, Zheng Chang, Jing Zhao, Juan Cui, Ying Xu, Liang Liu
Affiliations

A phylogenetic model for understanding the effect of gene duplication on cancer progression

Qin Ma et al. Nucleic Acids Res. 2014 Mar.

Abstract

As biotechnology advances rapidly, a tremendous amount of cancer genetic data has become available, providing an unprecedented opportunity for understanding the genetic mechanisms of cancer. To understand the effects of duplications and deletions on cancer progression, two genomes (normal and tumor) were sequenced from each of five stomach cancer patients in different stages (I, II, III and IV). We developed a phylogenetic model for analyzing stomach cancer data. The model assumes that duplication and deletion occur in accordance with a continuous time Markov Chain along the branches of a phylogenetic tree attached with five extended branches leading to the tumor genomes. Moreover, coalescence times of the phylogenetic tree follow a coalescence process. The simulation study suggests that the maximum likelihood approach can accurately estimate parameters in the phylogenetic model. The phylogenetic model was applied to the stomach cancer data. We found that the expected number of changes (duplication and deletion) per gene for the tumor genomes is significantly higher than that for the normal genomes. The goodness-of-fit test suggests that the phylogenetic model with constant duplication and deletion rates can adequately fit the duplication data for the normal genomes. The analysis found nine duplicated genes that are significantly associated with stomach cancer.

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Figures

Figure 1.
Figure 1.
The tree in the phylogenetic model. The normal genomes (N) at the tips of the tree are attached with five extended branches leading to the tumor genomes (T). Ni and Ti are the normal and tumor genomes of patient i. The tree (above normal genomes) represents the history of five normal genomes, while the extended branches represent the process leading to the five tumor genomes. The normal genomes are the ancestral genomes of the tumor genomes.
Figure 2.
Figure 2.
Simulation results. The square root of the mean square error for (a) estimating parameter m, and for (b) estimating parameter θ.
See this image and copyright information in PMC

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