Differential expression of selected histone modifier genes in human solid cancers

摘要: Post-translational modification of histones resulting in chromatin remodelling plays a key role the regulation gene expression. Here we report characteristic patterns expression 12 members 3 classes modifier genes 6 different cancer types: histone acetyltransferases (HATs)- EP300, CREBBP, and PCAF; deacetylases (HDACs)- HDAC1, HDAC2, HDAC4, HDAC5, HDAC7A, SIRT1; methyltransferases (HMTs)- SUV39H1 SUV39H2. Expression each 225 samples (135 primary tumours, 47 cell lines, 43 normal tissues) was analysedby QRT-PCR, normalized with 8 housekeeping genes, given as ratio by comparison universal reference RNA. This involved total 13,000 PCR assays allowing for rigorous analysis fitting linear regression model to data. Mutation SUV39H1, SUV39H2 revealed only two out 181 (both lines) significant coding-sequence alterations. Supervised Independent Component Analysis showed that many these able discriminate tumour from their counterparts. Clustering based on ratios also most were grouped according tissue type. Using discriminant classifier internal cross-validation few 5 SIRT1, HDAC5 PCAF, correctly assigned. The HATs, HDACs, HMTs suggest are important neoplastic transformation have depending origin, implications potential clinical application.