Gene Expression Profiling of Mismatch Repair Deficient Intestinal Stem Cells

We have generated a gene signature of mismatch repair (MMR) deficient intestinal stem cells (ISCs) using whole-genome transcriptomics and proteomics from murine intestinal stem cells and epithelial non-stem cells in a Lynch syndrome mouse model (Msh2-fl/fl;Villin-Cre). Then we have validated this signature in RNA-seq data from LS normal unaffected mucosa (UM), adenomas (AD) and adenomas with high-grade dsyplasia (AD-HGD) and tumors (T). MMR status for LS tumors and adenomas with high-grade dysplasia was categorized as KO, for unaffected mucosa as HET and FAP samples as WT. Overall design: We have performed mRNAseq using Illumina Hi-Seq in 3 mouse per genotype (9 total) and sequenced them in triplicated (total number of samples 18). 17 patients with FAP as controls (7 paired adenoma/mucosa samples and 10 unmatched normal mucosas) and 30 patients with LS (7 macthed tumor/adenomas with high-grade dysplasia and normal mucosa and 23 with normal mucosa only).