RT Journal Article
SR Electronic
T1 Integrative Genome-wide Analysis of the Determinants of RNA Splicing in Kidney Renal Clear Cell Carcinoma
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 010256
DO 10.1101/010256
A1 Kjong-Van Lehmann
A1 André Kahles
A1 Cyriac Kandoth
A1 William Lee
A1 Nikolaus Schultz
A1 Oliver Stegle
A1 Gunnar Rätsch
YR 2014
UL http://biorxiv.org/content/early/2014/10/19/010256.abstract
AB We present a genome-wide analysis of splicing patterns of 282 kidney renal clear cell carcinoma patients in which we integrate data from whole-exome sequencing of tumor and normal samples, RNA-seq and copy number variation. We proposed a scoring mechanism to compare splicing patterns in tumor samples to normal samples in order to rank and detect tumor-specific isoforms that have a potential for new biomarkers. We identified a subset of genes that show introns only observable in tumor but not in normal samples, ENCODE and GEUVADIS samples. In order to improve our understanding of the underlying genetic mechanisms of splicing variation we performed a large-scale association analysis to find links between somatic or germline variants with alternative splicing events. We identified 915 cis- and trans-splicing quantitative trait loci (sQTL) associated with changes in splicing patterns. Some of these sQTL have previously been associated with being susceptibility loci for cancer and other diseases. Our analysis also allowed us to identify the function of several COSMIC variants showing significant association with changes in alternative splicing. This demonstrates the potential significance of variants affecting alternative splicing events and yields insights into the mechanisms related to an array of disease phenotypes.