560 Transcriptome profiling in recessive dystrophic epidermolysis bullosa patients

Abstract

Recessive dystrophic epidermolysis bullosa (RDEB) represents the most severe subform of a rare skin disease family and is caused by mutations within the COL7A1 gene. Less abundant or dysfunctional type VII collagen impedes the structural integrity of the molecular link between epidermis and underlying dermis, which manifests in severe blister formation sublamina densa and erosions of skin and mucous membranes. RDEB patients suffer from chronically impaired wound healing and an extraordinary high risk of developing a particularly aggressive form of squamous cell carcinoma (SCC). In view of the need of treatment options for RDEB we have performed a transcriptomics case-control study on 36 primary cell lines to indentify new potential leads for future therapeutic approaches. More than 1,200 differentially expressed protein coding, and over 2,400 non-coding genes, including small RNAs, were identified. In contrast to RDEB keratinocytes more than 400 genes were not expressed in RDEB-SCC and over 1,100 genes were exclusively present in RDEB-SCC. A comparison of RDEB-SCC with non-RDEB SCC highlights an up-regulation of S100 family members amongst 300 differentially expressed genes. The evaluation of splice junction probe sets in RDEB-SCC compared to RDEB keratinocytes implied alternative splicing events in more than 200 protein coding and over 800 non-coding genes. Alternative splicing was indicated by at least one differentially expressed probe set region within exons or junction sites. Eventually our pool of de-regulated RNA in combination with alternative splicing events may provide the foundation for the analysis of pathomolecular events in regard of drugable targets.