title: Application of oncogenetic trees mixtures as a biostatistical model of the clonal cytogenetic evolution of meningiomas.
abstract: 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.
authors.affiliation: Department of Neurosurgery, Saarland University, Homburg/Saar, Germany. ncrket@uniklinik-saarland.de
authors.forename: Ralf
authors.initials: R
authors.lastname: Ketter
authors.forename: Steffi
authors.initials: S
authors.lastname: Urbschat
authors.forename: Wolfram
authors.initials: W
authors.lastname: Henn
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Feiden
authors.forename: Niko
authors.initials: N
authors.lastname: Beerenwinkel
authors.forename: Thomas
authors.initials: T
authors.lastname: Lengauer
authors.forename: Wolf-Ingo
authors.initials: WI
authors.lastname: Steudel
authors.forename: Klaus D
authors.initials: KD
authors.lastname: Zang
authors.forename: Jörg
authors.initials: J
authors.lastname: Rahnenführer
mesh_terms: D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations; D002892:Chromosomes, Human, Pair 22; D002999:Clone Cells; D003582:Cytogenetics / Q000379:methods; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D017353:Gene Deletion; D006801:Humans; D007621:Karyotyping; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D008579:Meningioma / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D008875:Middle Aged; D008957:Models, Genetic; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D012189:Retrospective Studies; D012737:Sex Factors; D013997:Time Factors; D016896:Treatment Outcome