A Gene Gravity Model for the Evolution of Cancer Genomes: A Study of 3,000 Cancer Genomes across 9 Cancer Types

PLoS Computational Biology
Feixiong ChengZhongming Zhao

Abstract

Cancer development and progression result from somatic evolution by an accumulation of genomic alterations. The effects of those alterations on the fitness of somatic cells lead to evolutionary adaptations such as increased cell proliferation, angiogenesis, and altered anticancer drug responses. However, there are few general mathematical models to quantitatively examine how perturbations of a single gene shape subsequent evolution of the cancer genome. In this study, we proposed the gene gravity model to study the evolution of cancer genomes by incorporating the genome-wide transcription and somatic mutation profiles of ~3,000 tumors across 9 cancer types from The Cancer Genome Atlas into a broad gene network. We found that somatic mutations of a cancer driver gene may drive cancer genome evolution by inducing mutations in other genes. This functional consequence is often generated by the combined effect of genetic and epigenetic (e.g., chromatin regulation) alterations. By quantifying cancer genome evolution using the gene gravity model, we identified six putative cancer genes (AHNAK, COL11A1, DDX3X, FAT4, STAG2, and SYNE1). The tumor genomes harboring the nonsynonymous somatic mutations in these genes had a higher mutation d...Continue Reading

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Citations

Nov 1, 2015·Nucleic Acids Research·Pora KimZhongming Zhao
Mar 31, 2016·Journal of the American Medical Informatics Association : JAMIA·Feixiong ChengZhongming Zhao
Nov 25, 2016·Scientific Reports·Youngjune ParkSun Kim
May 2, 2017·Briefings in Bioinformatics·Jiansong FangFeixiong Cheng
Dec 28, 2017·Journal of Molecular Cell Biology·Xing-Ming Zhao, Shan Li
Nov 16, 2017·PloS One·Kevin LaiSarah T Arron
Sep 28, 2017·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Laura Carrel, Carolyn J Brown
Jun 9, 2020·Briefings in Bioinformatics·Pora KimZhongming Zhao
Jan 23, 2019·Combinatorial Chemistry & High Throughput Screening·Yin WangLu Xie
Dec 3, 2016·Nucleic Acids Research·Pora KimZhongming Zhao
Apr 8, 2017·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Tenley C ArcherScott L Pomeroy
Sep 15, 2021·Orthodontics & Craniofacial Research·Tommaso GiliAntonella Polimeni
Sep 26, 2021·BMC Bioinformatics·Yun-Yun TangChun-Hou Zheng

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Methods Mentioned

BETA
exome sequencing
RNA-Seq

Software Mentioned

TCGA
Assembler
OncodriveCLUST
- Assembler
ActiveDriver
InnateDB
MutSig
R
OncodriveFM
Protein Interaction Network Analysis ( PINA ) platform

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