title: Integration of global spectral karyotyping, CGH arrays, and expression arrays reveals important genes in the pathogenesis of glioblastoma multiforme.
abstract: BACKGROUND
  Glioblastoma multiforme (GBM) is the most common primary tumor of the central nervous system in adults. Patients with GBM have few treatment options, and their disease is invariably fatal. Molecularly targeted agents offer the potential to improve patient treatment; however, the use of these will require a fuller understanding of the genetic changes in this complex tumor.
  
  
  METHODS
  We analyzed a series of 32 patients with GBM with array comparative genomic hybridization in combination with gene expression analysis. We focused on the recurrent breakpoints found by spectral karyotyping (SKY).
  
  
  RESULTS
  By SKY we identified 23 recurrent breakpoints of the 202 translocations found in GBM cases. Gains and losses were identified in chromosomal regions close to the breakpoints by array comparative genomic hybridization. We evaluated the genes located in the regions involved in the breakpoints in depth. A list of 406 genes that showed a level of expression significantly different between patients and control subjects was selected to determine their effect on survival. Genes CACNA2D3, PPP2R2B, SIK, MAST3, PROM1, and PPP6C were significantly associated with shorter survival (median 200 days vs. 450 days, P≤0.03).
  
  
  CONCLUSIONS
  We present a list of genes located in regions of breakpoints that could be grounds for future studies to determine whether they are crucial in the pathogenesis of this type of tumor, and we provide a list of six genes associated with the clinical outcome of patients with GBM.
authors.affiliation: Centro de Investigación del Cáncer, Universidad de Salamanca-CSIC, Salamanca, Spain. peleone@yahoo.com
authors.forename: Paola E
authors.initials: PE
authors.lastname: Leone
authors.forename: M Belén
authors.initials: MB
authors.lastname: González
authors.forename: Carolina
authors.initials: C
authors.lastname: Elosua
authors.forename: Juan A
authors.initials: JA
authors.lastname: Gómez-Moreta
authors.forename: Eva
authors.initials: E
authors.lastname: Lumbreras
authors.forename: Cristina
authors.initials: C
authors.lastname: Robledo
authors.forename: Angel
authors.initials: A
authors.lastname: Santos-Briz
authors.forename: José Maria
authors.initials: JM
authors.lastname: Valero
authors.forename: Rafael Díaz
authors.initials: RD
authors.lastname: de la Guardia
authors.forename: Norma C
authors.initials: NC
authors.lastname: Gutiérrez
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Hernández
authors.forename: Juan L
authors.initials: JL
authors.lastname: García
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D005260:Female; D020869:Gene Expression Profiling; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D032681:Spectral Karyotyping; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger