Differential gene expression in human cerebrovascular malformations.
OBJECTIVE
We sought to identify genes with differential expression in cerebral cavernous malformations (CCMs), arteriovenous malformations (AVMs), and control superficial temporal arteries (STAs) and to confirm differential expression of genes previously implicated in the pathobiology of these lesions.


METHODS
Total ribonucleic acid was isolated from four CCM, four AVM, and three STA surgical specimens and used to quantify lesion-specific messenger ribonucleic acid expression levels on human gene arrays. Data were analyzed with the use of two separate methodologies: gene discovery and confirmation analysis.


RESULTS
The gene discovery method identified 42 genes that were significantly up-regulated and 36 genes that were significantly down-regulated in CCMs as compared with AVMs and STAs (P = 0.006). Similarly, 48 genes were significantly up-regulated and 59 genes were significantly down-regulated in AVMs as compared with CCMs and STAs (P = 0.006). The confirmation analysis showed significant differential expression (P < 0.05) in 11 of 15 genes (angiogenesis factors, receptors, and structural proteins) that previously had been reported to be expressed differentially in CCMs and AVMs in immunohistochemical analysis.


CONCLUSIONS
We identify numerous genes that are differentially expressed in CCMs and AVMs and correlate expression with the immunohistochemistry of genes implicated in cerebrovascular malformations. In future efforts, we will aim to confirm candidate genes specifically related to the pathobiology of cerebrovascular malformations and determine their biological systems and mechanistic relevance.
Shenkar
Robert
R
Center for Cellular and Molecular Neurosurgery, Department of Neurosurgery, University of Colorado Health Sciences Center, Denver, Colorado, USA.
Elliott
J Paul
JP
Diener
Katrina
K
Gault
Judith
J
Hu
Ling-Jia
LJ
Cohrs
Randall J
RJ
Phang
Tzulip
T
Hunter
Lawrence
L
Breeze
Robert E
RE
Awad
Issam A
IA
D000293:Adolescent; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002648:Child; D003337:Corpus Callosum / Q000473:pathology; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D015870:Gene Expression / Q000502:physiology*; D006392:Hemangioma, Cavernous / Q000235:genetics* / Q000473:pathology; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D013699:Temporal Arteries / Q000473:pathology; D013702:Temporal Lobe / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics
D012333:RNA, Messenger