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Kjong-Van Lehmann

Publications and source records attributed to Kjong-Van Lehmann.

2 recordsLinked to original sources

Integrative Analysis of Transcriptome Variation in Uterine Carcinosarcoma and Comparison to Sarcoma and Endometrial Carcinoma

Large-scale cancer genomics has made a huge impact onto cancer research. It has allowed the characterization of tumor types in an unprecedented depth. More recent studies target the joint analysis of multiple tumor types to gain insight into similarities and differences on a molecular level. Here we present an analysis of Uterine Carcinosarcoma. The histological similarities to sarcomas and carcinomas warrants an in-depth analysis to Uterine Endometrial Carcinoma as well as Sarcomas and we have used data from The Cancer Genome Atlas to understand transcriptome similarities and differences between these tumor types. We have performed a differential transcriptome analysis of Uterine Carinosarcoma to Uterine samples from GTEx to find genes with tumor specific splicing or expression patterns, which may not only be of interest for a deeper mechanistic understanding of the development and progression of Uterine Carcinosarcoma, but may also be potential tumor markers. Similarities and differences to Sarcomas and Endometrial Carcinomas present new opportunities for the development of new and targeted drug therapies. Finally we have also studied genetic determinants of gene expression and splicing changes and identified germline variants that explain expression and splicing differences between individuals. This analysis demonstrates the opportunities of integrative comparative analysis between multiple tumor types.

Cancer Biology

Integrative Genome-wide Analysis of the Determinants of RNA Splicing in Kidney Renal Clear Cell Carcinoma

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.

Cancer Biology