The first three authors contributed equally to the present work and are listed alphabetically.
Gene Expression Analysis of Tuberous Sclerosis Complex Cortical Tubers Reveals Increased Expression of Adhesion and Inflammatory Factors
Article first published online: 8 OCT 2009
© 2009 The Authors. Journal Compilation © 2009 International Society of Neuropathology
Volume 20, Issue 4, pages 704–719, July 2010
How to Cite
Boer, K., Crino, P. B., Gorter, J. A., Nellist, M., Jansen, F. E., Spliet, W. G.M., Van Rijen, P. C., Wittink, F. R.A., Breit, T. M., Troost, D., Wadman, W. J. and Aronica, E. (2010), Gene Expression Analysis of Tuberous Sclerosis Complex Cortical Tubers Reveals Increased Expression of Adhesion and Inflammatory Factors. Brain Pathology, 20: 704–719. doi: 10.1111/j.1750-3639.2009.00341.x
- Issue published online: 7 JUN 2010
- Article first published online: 8 OCT 2009
- Received 28 July 2009; revised 24 September 2009; accepted 2 October 2009.
- cell adhesion;
- cortical tubers;
Cortical tubers in patients with tuberous sclerosis complex are associated with disabling neurological manifestations, including intractable epilepsy. While these malformations are believed to result from the effects of TSC1 or TSC2 gene mutations, the molecular mechanisms leading to tuber formation, as well as the onset of seizures, remain largely unknown. We used the Affymetrix Gene Chip platform to provide the first genome-wide investigation of gene expression in surgically resected tubers, compared with histological normal perituberal tissue from the same patients or autopsy control tissue. We identified 2501 differentially expressed genes in cortical tubers compared with autopsy controls. Expression of genes associated with cell adhesion, for example, VCAM1, integrins and CD44, or with the inflammatory response, including complement factors, serpinA3, CCL2 and several cytokines, was increased in cortical tubers, whereas genes related to synaptic transmission, for example, the glial glutamate transporter GLT-1, and voltage-gated channel activity, exhibited lower expression. Gene expression in perituberal cortex was distinct from autopsy control cortex suggesting that even in the absence of tissue pathology the transcriptome is altered in TSC. Changes in gene expression yield insights into new candidate genes that may contribute to tuber formation or seizure onset, representing new targets for potential therapeutic development.