Article first published online: 7 JUN 2007
Copyright © 2007 Wiley-Liss, Inc.
International Journal of Cancer
Volume 121, Issue 7, pages 1473–1480, 1 October 2007
How to Cite
Ketter, R., Urbschat, S., Henn, W., Feiden, W., Beerenwinkel, N., Lengauer, T., Steudel, W.-I., Zang, K. D. and Rahnenführer, J. (2007), Application of oncogenetic trees mixtures as a biostatistical model of the clonal cytogenetic evolution of meningiomas. Int. J. Cancer, 121: 1473–1480. doi: 10.1002/ijc.22855
Availability: Mtreemix, a software package for estimating trees mixtures models, is freely available for noncommercial users at http://mtreemix. bioinf.mpi-inf.mpg.de. The raw cancer datasets and R code for the analysis with Cox models are available upon request from the corresponding author.
The work at the Max–Planck-Institute for Informatics was performed in the context of the BioSapiens Network of Excellence (EU contact no. LSHG-CT-2003-503265).
- Issue published online: 24 JUL 2007
- Article first published online: 7 JUN 2007
- Manuscript Accepted: 11 APR 2007
- Manuscript Received: 22 DEC 2006
- BMBF. Grant Number: 01GR0453
- HomFor. Grant Number: 68-06
- oncogenetic trees;
- genetic progression score
Meningiomas are mostly benign tumors that originate from the coverings of brain and spinal cord. Typically, they reveal a normal karyotype or monosomy for chromosome 22. Rare clinical progression of meningiomas is associated with a nonrandom pattern of secondary losses of other autosomes. Deletion of the short arm of one chromosome 1 appears to be a decisive step for anaplastic growth in meningiomas. We calculated an oncogenetic tree model that estimates the most likely cytogenetic pathways of 661 meningioma patients in terms of accumulation of somatic chromosome changes in tumor cells. The genetic progression score (GPS) estimates the genetic status of a tumor as progression in the corresponding tumor cells along this model. Large GPS values are highly correlated with early recurrence of meningiomas [p < 10−4]. This correlation holds even if patients are stratified by WHO grade. We show that tumor location also has an impact on genetic progression. Clinical relevance of the GPS is thus demonstrated with respect to origin, WHO grade and recurrence of the tumor. As a quantitative measure the GPS allows a more precise assessment of the prognosis of meningiomas than categorical cytogenetic markers based on single chromosomal aberrations. © 2007 Wiley-Liss, Inc.