Differential gene expression in human cerebrovascular malformations

Robert Shenkar, J. Paul Elliott, Katrina Diener, Judith Gault, Ling Jia Hu, Randall J. Cohrs, Tzulip Phang, Lawrence Hunter, Robert E. Breeze, Issam A. Awad, Charles J. Hodge, Robert J. Dempsey, Maciej S. Lesniak, Daniele Rigamonti, Robert L. Dodd, Gary K. Steinberg, James T. Rutka

Research output: Contribution to journalArticle

Abstract

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. CONCLUSION: 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.

Original languageEnglish (US)
Pages (from-to)465-478
Number of pages14
JournalNeurosurgery
Volume52
Issue number2
StatePublished - Feb 1 2003
Externally publishedYes

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Central Nervous System Cavernous Hemangioma
Arteriovenous Malformations
Gene Expression
Temporal Arteries
Genes
Genetic Association Studies
RNA
Angiogenesis Inducing Agents
Immunohistochemistry

Keywords

  • Arteriovenous malformations
  • Cavernous malformations
  • Gene arrays
  • Gene expression

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

Cite this

Shenkar, R., Elliott, J. P., Diener, K., Gault, J., Hu, L. J., Cohrs, R. J., ... Rutka, J. T. (2003). Differential gene expression in human cerebrovascular malformations. Neurosurgery, 52(2), 465-478.

Differential gene expression in human cerebrovascular malformations. / Shenkar, Robert; Elliott, J. Paul; Diener, Katrina; Gault, Judith; Hu, Ling Jia; Cohrs, Randall J.; Phang, Tzulip; Hunter, Lawrence; Breeze, Robert E.; Awad, Issam A.; Hodge, Charles J.; Dempsey, Robert J.; Lesniak, Maciej S.; Rigamonti, Daniele; Dodd, Robert L.; Steinberg, Gary K.; Rutka, James T.

In: Neurosurgery, Vol. 52, No. 2, 01.02.2003, p. 465-478.

Research output: Contribution to journalArticle

Shenkar, R, Elliott, JP, Diener, K, Gault, J, Hu, LJ, Cohrs, RJ, Phang, T, Hunter, L, Breeze, RE, Awad, IA, Hodge, CJ, Dempsey, RJ, Lesniak, MS, Rigamonti, D, Dodd, RL, Steinberg, GK & Rutka, JT 2003, 'Differential gene expression in human cerebrovascular malformations', Neurosurgery, vol. 52, no. 2, pp. 465-478.
Shenkar R, Elliott JP, Diener K, Gault J, Hu LJ, Cohrs RJ et al. Differential gene expression in human cerebrovascular malformations. Neurosurgery. 2003 Feb 1;52(2):465-478.
Shenkar, Robert ; Elliott, J. Paul ; Diener, Katrina ; Gault, Judith ; Hu, Ling Jia ; Cohrs, Randall J. ; Phang, Tzulip ; Hunter, Lawrence ; Breeze, Robert E. ; Awad, Issam A. ; Hodge, Charles J. ; Dempsey, Robert J. ; Lesniak, Maciej S. ; Rigamonti, Daniele ; Dodd, Robert L. ; Steinberg, Gary K. ; Rutka, James T. / Differential gene expression in human cerebrovascular malformations. In: Neurosurgery. 2003 ; Vol. 52, No. 2. pp. 465-478.
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abstract = "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. CONCLUSION: 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.",
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T1 - Differential gene expression in human cerebrovascular malformations

AU - Shenkar, Robert

AU - Elliott, J. Paul

AU - Diener, Katrina

AU - Gault, Judith

AU - Hu, Ling Jia

AU - Cohrs, Randall J.

AU - Phang, Tzulip

AU - Hunter, Lawrence

AU - Breeze, Robert E.

AU - Awad, Issam A.

AU - Hodge, Charles J.

AU - Dempsey, Robert J.

AU - Lesniak, Maciej S.

AU - Rigamonti, Daniele

AU - Dodd, Robert L.

AU - Steinberg, Gary K.

AU - Rutka, James T.

PY - 2003/2/1

Y1 - 2003/2/1

N2 - 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. CONCLUSION: 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.

AB - 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. CONCLUSION: 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.

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KW - Cavernous malformations

KW - Gene arrays

KW - Gene expression

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