Title
An Evolutionary Approach for Identifying Driver Mutations in Colorectal Cancer
Abstract
The traditional view of cancer as a genetic disease that can successfully be treated with drugs targeting mutant onco-proteins has motivated whole-genome sequencing efforts in many human cancer types. However, only a subset of mutations found within the genomic landscape of cancer is likely to provide a fitness advantage to the cell. Distinguishing such "driver" mutations from innocuous "passenger" events is critical for prioritizing the validation of candidate mutations in disease-relevant models. We design a novel statistical index, called the Hitchhiking Index, which reflects the probability that any observed candidate gene is a passenger alteration, given the frequency of alterations in a cross-sectional cancer sample set, and apply it to a mutational data set in colorectal cancer. Our methodology is based upon a population dynamics model of mutation accumulation and selection in colorectal tissue prior to cancer initiation as well as during tumorigenesis. This methodology can be used to aid in the prioritization of candidate mutations for functional validation and contributes to the process of drug discovery.
Year
DOI
Venue
2015
10.1371/journal.pcbi.1004350
PLOS COMPUTATIONAL BIOLOGY
Field
DocType
Volume
Carcinogenesis,Population,Disease,Candidate gene,Biology,Point mutation,Bioinformatics,Genetics,Colorectal cancer,Cancer,Mutation
Journal
11
Issue
ISSN
Citations 
9
1553-7358
8
PageRank 
References 
Authors
0.76
5
7
Name
Order
Citations
PageRank
Jasmine Foo112911.02
Lin L. Liu280.76
Kevin Leder3133.12
Markus Riester4253.04
yoh iwasa5243.39
Christoph Lengauer680.76
Franziska Michor74713.04