Gene Microarray Analysis of Human Brain Arteriovenous Malformations

Tomoki Hashimoto, Michael T. Lawton, Gen Wen, Guo Yuan Yang, Thomas Chaly, Campbell L. Stewart, Holly K. Dressman, Nicholas Barbaro, Douglas A. Marchuk, William L. Young, Charles J. Hodge, Matthias Kirsch, Gabriele Schackert, Robert L. Dodd, Gary K. Steinberg, Nobutake Sadamasa, Kazuhiko Nozaki, Nobuo Hashimoto, Charles Matouk, James T. Rutka

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

OBJECTIVE: Human brain arteriovenous malformations (BAVMs) display abnormal expression of various angiogenesis-related genes and their products. We examined gene expression patterns in BAVMs by the gene microarray technique. METHODS: We analyzed BAVM and control brain samples obtained by temporal lobectomy for medically intractable seizure by Affymetrix Human Gene Set U95Av2 (Affymetrix, Inc., Santa Clara, CA). The gene microarray data were compared with new and previously published data that used conventional molecular biology techniques. RESULTS: We analyzed six BAVM and five control brain samples. From 12,625 gene probes assayed, 1781 gene probes showed differential expression between BAVMs and controls. BAVM samples had a gene expression pattern that was distinct from those of control brain samples. Increased messenger ribonucleic acid expression of vascular endothelial growth factor A was accompanied by increased expression of its protein product. A majority of the gene data was in agreement with previously published data. The gene microarray data generated a new testable hypothesis regarding integrin, and we found increased expression of integrin αvβ3 protein in BAVMs. CONCLUSION: The gene expression pattern of BAVMs was distinct from those of control brain samples. We verified the gene microarray data by demonstrating that increased gene expression levels for angiogenesis-related molecules were accompanied by increased levels of their protein product expression. The gene microarray technique may be a useful tool to study multiple pathways simultaneously in BAVM specimens.

Original languageEnglish (US)
Pages (from-to)410-425
Number of pages16
JournalNeurosurgery
Volume54
Issue number2
StatePublished - Feb 2004
Externally publishedYes

Fingerprint

Arteriovenous Malformations
Microarray Analysis
Brain
Genes
Gene Expression
Integrins
Proteins
Vascular Endothelial Growth Factor A
Molecular Biology
Seizures

Keywords

  • Angiogenesis
  • Cerebral arteriovenous malformations
  • Gene expression
  • Integrin αvβ3
  • Oligonucleotide array sequence analysis
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

Cite this

Hashimoto, T., Lawton, M. T., Wen, G., Yang, G. Y., Chaly, T., Stewart, C. L., ... Rutka, J. T. (2004). Gene Microarray Analysis of Human Brain Arteriovenous Malformations. Neurosurgery, 54(2), 410-425.

Gene Microarray Analysis of Human Brain Arteriovenous Malformations. / Hashimoto, Tomoki; Lawton, Michael T.; Wen, Gen; Yang, Guo Yuan; Chaly, Thomas; Stewart, Campbell L.; Dressman, Holly K.; Barbaro, Nicholas; Marchuk, Douglas A.; Young, William L.; Hodge, Charles J.; Kirsch, Matthias; Schackert, Gabriele; Dodd, Robert L.; Steinberg, Gary K.; Sadamasa, Nobutake; Nozaki, Kazuhiko; Hashimoto, Nobuo; Matouk, Charles; Rutka, James T.

In: Neurosurgery, Vol. 54, No. 2, 02.2004, p. 410-425.

Research output: Contribution to journalArticle

Hashimoto, T, Lawton, MT, Wen, G, Yang, GY, Chaly, T, Stewart, CL, Dressman, HK, Barbaro, N, Marchuk, DA, Young, WL, Hodge, CJ, Kirsch, M, Schackert, G, Dodd, RL, Steinberg, GK, Sadamasa, N, Nozaki, K, Hashimoto, N, Matouk, C & Rutka, JT 2004, 'Gene Microarray Analysis of Human Brain Arteriovenous Malformations', Neurosurgery, vol. 54, no. 2, pp. 410-425.
Hashimoto T, Lawton MT, Wen G, Yang GY, Chaly T, Stewart CL et al. Gene Microarray Analysis of Human Brain Arteriovenous Malformations. Neurosurgery. 2004 Feb;54(2):410-425.
Hashimoto, Tomoki ; Lawton, Michael T. ; Wen, Gen ; Yang, Guo Yuan ; Chaly, Thomas ; Stewart, Campbell L. ; Dressman, Holly K. ; Barbaro, Nicholas ; Marchuk, Douglas A. ; Young, William L. ; Hodge, Charles J. ; Kirsch, Matthias ; Schackert, Gabriele ; Dodd, Robert L. ; Steinberg, Gary K. ; Sadamasa, Nobutake ; Nozaki, Kazuhiko ; Hashimoto, Nobuo ; Matouk, Charles ; Rutka, James T. / Gene Microarray Analysis of Human Brain Arteriovenous Malformations. In: Neurosurgery. 2004 ; Vol. 54, No. 2. pp. 410-425.
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AU - Lawton, Michael T.

AU - Wen, Gen

AU - Yang, Guo Yuan

AU - Chaly, Thomas

AU - Stewart, Campbell L.

AU - Dressman, Holly K.

AU - Barbaro, Nicholas

AU - Marchuk, Douglas A.

AU - Young, William L.

AU - Hodge, Charles J.

AU - Kirsch, Matthias

AU - Schackert, Gabriele

AU - Dodd, Robert L.

AU - Steinberg, Gary K.

AU - Sadamasa, Nobutake

AU - Nozaki, Kazuhiko

AU - Hashimoto, Nobuo

AU - Matouk, Charles

AU - Rutka, James T.

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N2 - OBJECTIVE: Human brain arteriovenous malformations (BAVMs) display abnormal expression of various angiogenesis-related genes and their products. We examined gene expression patterns in BAVMs by the gene microarray technique. METHODS: We analyzed BAVM and control brain samples obtained by temporal lobectomy for medically intractable seizure by Affymetrix Human Gene Set U95Av2 (Affymetrix, Inc., Santa Clara, CA). The gene microarray data were compared with new and previously published data that used conventional molecular biology techniques. RESULTS: We analyzed six BAVM and five control brain samples. From 12,625 gene probes assayed, 1781 gene probes showed differential expression between BAVMs and controls. BAVM samples had a gene expression pattern that was distinct from those of control brain samples. Increased messenger ribonucleic acid expression of vascular endothelial growth factor A was accompanied by increased expression of its protein product. A majority of the gene data was in agreement with previously published data. The gene microarray data generated a new testable hypothesis regarding integrin, and we found increased expression of integrin αvβ3 protein in BAVMs. CONCLUSION: The gene expression pattern of BAVMs was distinct from those of control brain samples. We verified the gene microarray data by demonstrating that increased gene expression levels for angiogenesis-related molecules were accompanied by increased levels of their protein product expression. The gene microarray technique may be a useful tool to study multiple pathways simultaneously in BAVM specimens.

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KW - Gene expression

KW - Integrin αvβ3

KW - Oligonucleotide array sequence analysis

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