Disrupted gene expression in human cerebral cavernous malformations (1123.3)

Abstract

CCM is a serious human disease affecting 35 million people worldwide, characterized by grossly dilated brain capillaries forming clustered caverns. CCM is caused by familial (inheritable) mutations in KRIT1, CCM2 or PDCD10 genes, or sporadic occurrence of unknown origin. Hemorrhagic stroke may occur and symptomatic lesions are removed surgically since no drug therapy exists. All three CCM genes are expressed in all tissues, so inherited mutations might be expected to produce vascular lesions everywhere. Instead CCMs are confined to the brain, suggesting there are brain capillary‐specific additional genetic disruptions contributing to CCM pathology. My project focuses on assessing expression of target genes in CCM endothelial cells to identify commonly deregulated genes in both familial and sporadic CCMs. I purified RNA from resected human tissue, then performed Reverse‐Transcription PCR to synthesize a cDNA library representing differential expression between sample and control normal endothelial cells. We conducted gene expression studies first by microarray to identify target genes, then validation using quantitative PCR (qPCR) to compare normal and diseased tissue, to determine statistically significant changes in CCM samples. We find disruptions in functional GO cluster groups including apoptosis and matrix synthesis.Grant Funding Source: NIH