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Gene expression analysis of tuberous sclerosis complex cortical tubers reveals increased expression of adhesion and inflammatory factors.

ABSTRACT: 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.

SUBMITTER: Boer K

PROVIDER: S-EPMC2888867 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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Gene expression analysis of tuberous sclerosis complex cortical tubers reveals increased expression of adhesion and inflammatory factors.

Boer Karin K Crino Peter B PB Gorter Jan A JA Nellist Mark M Jansen Floor E FE Spliet Wim G M WG van Rijen Peter C PC Wittink Floyd R A FR Breit Timo M TM Troost Dirk D Wadman Wytse J WJ Aronica Eleonora E

Brain pathology (Zurich, Switzerland) 20091008 4

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, c ...[more]

PMID: 19912235

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Project description:Introduction and importance Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by inactivating mutations in TSC1 or TSC2 genes, resulting in benign lesions that involve multiple organs including the central nerves system. Case presentation A 39-year-old male of known TSC presented with inability to walk for two months. On physical examination, he was consciously oriented and cooperative, but he had spastic tetraparesis in the muscle-motor examination. On brain imaging, cystic lesions of various sizes in the supra and infratentorial regions were observed, consistent with giant cyst-like tubers. However, they could not differentiate from TSC related brain tumors based on the imaging findings. He underwent surgical intervention to resect/evacuate the large cystic lesion, which had the mass effects on the brain stem. The pathologic examinations revealed no malignant changes. Clinical discussion Although the cyst-like lesions in the cortex and white matter have been reported in several previous studies of TSC, they usually had a small size and similar intensity to CSF on T2- weighted MRI and low intensity on FLAIR images. Conclusion Giant cyst-like cortical tubers are exceedingly rare and atypical findings of tuberous sclerosis complex, which are usually associated with epilepsy and neurological deficits. Though many authors recommend the brain MRI as a screening tool for patients with TSC once every 1–3 years until the age of 25, our report showed that the brain lesions may develop in patients with TSC even after the age of 25. Thus, the MRI should be used periodically in all patients with TSC to timely detect the brain lesions and prevent the patient's disability. Surgical resection is the mainstay of treatment for the symptomatic cystic-like cortical tuber; however, it may recur after resection. Highlights • Giant cyst-like cortical tubers are rare and atypical findings of tuberous sclerosis complex.• They are usually associated with epilepsy and neurological deficits.• MRI should be used periodically in all patients with tuberous sclerosis complex to timely detect the brain lesions.• Surgical resection is the mainstay of treatment. However, these lesions may recur after resection.

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Gene expression analysis of tuberous sclerosis complex cortical tubers reveals increased expression of adhesion and inflammatory factors.

Publications

Gene expression analysis of tuberous sclerosis complex cortical tubers reveals increased expression of adhesion and inflammatory factors.

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