Genomic profiling reveals alternative genetic pathways of meningioma malignant progression dependent on the underlying NF2 status.
OBJECTIVE
Meningiomas are the most common central nervous system tumors in the population of age 35 and older. WHO defines three grades predictive of the risk of recurrence. Clinical data supporting histologic malignant progression of meningiomas are sparse and underlying molecular mechanisms are not clearly depicted.


METHODS
We identified genetic alterations associated with histologic progression of 36 paired meningioma samples in 18 patients using 500K SNP genotyping arrays and NF2 gene sequencing.


RESULTS
The most frequent chromosome alterations observed in progressing meningioma samples are early alterations (i.e., present both in lower- and higher-grade samples of a single patient). In our series, NF2 gene inactivation was an early and frequent event in progressing meningioma samples (73%). Chromosome alterations acquired during progression from grade I to grade II meningioma were not recurrent. Progression to grade III was characterized by recurrent genomic alterations, the most frequent being CDKN2A/CDKN2B locus loss on 9p.


CONCLUSIONS
Meningiomas displayed different patterns of genetic alterations during progression according to their NF2 status: NF2-mutated meningiomas showed higher chromosome instability during progression than NF2-nonmutated meningiomas, which had very few imbalanced chromosome segments. This pattern of alterations could thus be used as markers in clinical practice to identify tumors prone to progress among grade I meningiomas.
Goutagny
Stéphane
S
Université Paris 5-Descartes, Paris, France.
Yang
Hong Wei
HW
Zucman-Rossi
Jessica
J
Chan
Jennifer
J
Dreyfuss
Jonathan M
JM
Park
Peter J
PJ
Black
Peter M
PM
Giovannini
Marco
M
Carroll
Rona S
RS
Kalamarides
Michel
M
D000328:Adult; D000368:Aged; D018450:Disease Progression; D005260:Female; D018628:Gene Dosage; D015870:Gene Expression; D020869:Gene Expression Profiling; D016515:Genes, Neurofibromatosis 2; D005838:Genotype; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000473:pathology*; D008579:Meningioma / Q000235:genetics* / Q000473:pathology*; D008875:Middle Aged; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction