Title
Estimating cancer survival and clinical outcome based on genetic tumor progression scores.
Abstract
In cancer research, prediction of time to death or relapse is important for a meaningful tumor classification and selecting appropriate therapies. Survival prognosis is typically based on clinical and histological parameters. There is increasing interest in identifying genetic markers that better capture the status of a tumor in order to improve on existing predictions. The accumulation of genetic alterations during tumor progression can be used for the assessment of the genetic status of the tumor. For modeling dependences between the genetic events, evolutionary tree models have been applied.Mixture models of oncogenetic trees provide a probabilistic framework for the estimation of typical pathogenetic routes. From these models we derive a genetic progression score (GPS) that estimates the genetic status of a tumor. GPS is calculated for glioblastoma patients from loss of heterozygosity measurements and for prostate cancer patients from comparative genomic hybridization measurements. Cox proportional hazard models are then fitted to observed survival times of glioblastoma patients and to times until PSA relapse following radical prostatectomy of prostate cancer patients. It turns out that the genetically defined GPS is predictive even after adjustment for classical clinical markers and thus can be considered a medically relevant prognostic factor.Mtreemix, a software package for estimating tree mixture models, is freely available for non-commercial users at http://mtreemix.bioinf.mpi-sb.mpg.de. The raw cancer datasets and R code for the analysis with Cox models are available upon request from the corresponding author.
Year
DOI
Venue
2005
10.1093/bioinformatics/bti312
Bioinformatics
Keywords
Field
DocType
cancer research,prostate cancer patient,genetic marker,meaningful tumor classification,genetic progression score,genetic status,genetic alteration,clinical outcome,estimating cancer survival,genetic tumor progression score,genetic event,tumor progression,glioblastoma patient,loss of heterozygosity,evolutionary trees,cox model,mixture model,genetics
Tumor progression,Proportional hazards model,Computer science,Comparative genomic hybridization,Genetic Status,Prostatectomy,Prostate cancer,Bioinformatics,Cancer,Genetic marker
Journal
Volume
Issue
ISSN
21
10
1367-4803
Citations 
PageRank 
References 
14
1.69
2
Authors
7
Name
Order
Citations
PageRank
Jörg Rahnenführer159438.14
Niko Beerenwinkel2696102.47
Wolfgang A Schulz3141.69
Christian Hartmann4141.69
Andreas von Deimling5172.57
Bernd Wullich6274.97
Thomas Lengauer73155605.03