Distinct genetic signatures among pilocytic astrocytomas relate to their brain region origin.
Pilocytic astrocytomas (PAs) are the most common glioma in children. Whereas many PAs are slow-growing or clinically indolent, others exhibit more aggressive features with tumor recurrence and death. To identify genetic signatures that might predict PA clinical behavior, we did gene expression profiling on 41 primary PAs arising sporadically and in patients with neurofibromatosis type 1 (NF1). Whereas no expression signature was found that could discriminate clinically aggressive or recurrent tumors from more indolent cases, PAs arising in patients with NF1 did exhibit a unique gene expression pattern. In addition, we identified a gene expression signature that stratified PAs by location (supratentorial versus infratentorial). Lastly, we also identified a gene expression pattern common to PAs and normal mouse astrocytes and neural stem cells from these distinct brain regions as well as a gene expression pattern shared between PAs and another human glial tumor (ependymoma) arising supratentorially compared with those originating in the posterior fossa. These results suggest that glial tumors share an intrinsic, lineage-specific molecular signature that reflects the brain region in which their nonmalignant predecessors originated.
Sharma
Mukesh K
MK
Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Mansur
David B
DB
Reifenberger
Guido
G
Perry
Arie
A
Leonard
Jeffrey R
JR
Aldape
Kenneth D
KD
Albin
Meredith G
MG
Emnett
Ryan J
RJ
Loeser
Simon
S
Watson
Mark A
MA
Nagarajan
Rakesh
R
Gutmann
David H
DH
D000293:Adolescent; D000328:Adult; D000465:Algorithms; D001254:Astrocytoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D015192:Infratentorial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009456:Neurofibromatosis 1 / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D015173:Supratentorial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology