title: Low-level amplification of oncogenes correlates inversely with age for patients with nontypical meningiomas.
abstract: BACKGROUND
  This study sought to identify genes in nontypical meningiomas with gains in copy number (CN) that correlate with earlier age of onset, an indicator of aggressiveness.
  
  
  METHODS
  Among 94 adult patients, 91 had 105 meningiomas that were histologically confirmed. World Health Organization grades I (typical), II (atypical), and III (anaplastic) were assigned to tumors in 76, 14, and 1 patient, respectively. Brain invasion indicated that two World Health Organization grade I meningiomas were biologically atypical. DNA from 15 invasive/atypical/anaplastic meningiomas and commercial normal DNA were analyzed with multiplex ligation dependent probe amplification. The CN ratios (fold differences from normal) for 78 genes were determined. The CN ratio was defined as [tumor CN]/[normal CN] for each gene to normalize results.
  
  
  RESULTS
  Characteristic gene losses (CN ratio < 0.75) occurred in >50% of the invasive/atypical/anaplastic meningiomas at 22q11, 1p34.2, and 1p22.1 loci. Gains (CN ratio ≥ 2.0) occurred in each tumor for 2 or more of 19 genes. Each of the 19 genes' CN ratio was ≥ 2.0 in multiple tumors, and their collective sums (up to 49.1) correlated inversely with age (r = -0.72), minus an outlier. In patients ≤ 55 versus >55 years, 5 genes (BIRC2, BRAF, MET, NRAS, and PIK3CA) individually exhibited significantly higher CN ratios (P < 0.05) or a trend for them (P < 0.09), with corrections for multiple comparisons, and their sums correlated inversely with age (r = -0.74).
  
  
  CONCLUSIONS
  Low levels of amplification for selected oncogenes in invasive/atypical/anaplastic meningiomas were higher in younger adults, with the CN gains potentially underlying biological aggressiveness associated with early tumor development.
authors: Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA. mbeckn@lsuhsc.edu
authors: Marie E
authors: ME
authors: Beckner
authors: Raghuram
authors: R
authors: Sampath
authors: Ashley B
authors: AB
authors: Flowers
authors: Kristopher
authors: K
authors: Katira
authors: Dwain
authors: D
authors: D'Souza
authors: Shashikant
authors: S
authors: Patil
authors: Raj B
authors: RB
authors: Patel
authors: Mary L
authors: ML
authors: Nordberg
authors: Anil
authors: A
authors: Nanda
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D018628:Gene Dosage; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D008579:Meningioma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009857:Oncogenes / Q000235:genetics*; D055815:Young Adult