RNA over-editing leads to aggressiveness of intrahepatic cholangiocarcinoma [SNP]

Alteration in RNA editing has been connected to tumor progression and many other important human diseases. However, the role of RNA editing in intrahepatic cholangiocarcinoma (ICC) remains unclear. Here we conducted a transcriptome-wide investigation in ICCs, and revealed ADAR-associated over-editing occurred uniformly in ICCs. Collectively, these results reveal a previously unrecognized role of RNA editing in malignant transformation into ICC, and ADAR1 inhibition may obviate progression and relapse of this malignancy. To detect copy number variations (CNVs) for the 15 ICCs in discovery stage, we performed genome-wide single nucleotide polymorphisms (SNPs) genotyping by Affymetrix Genome-Wide Human SNP Array 6.0, which includes more than 906,600 single nucleotide polymorphisms (SNPs) and more than 946,000 probes. Copy-number estimation using Robust Multichip Analysis (CRMA, v2) method was used to pre-process the probe signal intensities from each raw .CEL file. This procedure consists of a calibration for offset and global crosstalk between alleles, and normalized for probe sequence effects. Once the data has been preprocessed using CRMA, fragment-length effects were normalized. Next, raw copy numbers was calculated by paired analysis, which takes the matched non-tumor liver tissue as reference for each tumor. Segmented copy number profiles were analyzed using Circular binary segmentation (CBS) algorithm with default parameters in the R package “DNA-copy”.