Research scientist Dr. Margarete Odenthal leads the translational molecular pathology group at University Hospital Cologne, putting new technologies through their paces to determine which ones best fit the needs and workflows of the diagnostics lab. Recently, she has worked closely with QIAGEN to assess sample extraction, target enrichment, and library preparation kits as well as data analysis and interpretation tools in a variety of cancer studies.
In one NGS-based study, she and her team analyzed BRCA1 and BRCA2 mutations in samples from severe ovarian cancer using QIAGEN products for library preparation, amplicon sequencing, and data analysis. Odenthal began with macrodissected FFPE ovarian cancer samples, which carried known germline point mutations or large deletions in the BRCA genes, using the GeneRead DNAseq Targeted Panels for human BRCA1 and BRCA2 exons for target enrichment. After sequencing, results were analyzed with Biomedical Genomics Workbench to identify somatic pathogenic mutations. “We used the copy number variation tool in order to see big deletions in the BRCA1 and BRCA2 genes,” Odenthal says. “Normally you don’t see these deletions very easily, so people have found this quite interesting.” By using the analysis tool to detect large deletions, her team is able to quickly evaluate pathogenic mutations likely to damage the protein.
In other work, she has been focused on new approaches to make sense of tumor activity that cannot be explained by DNA mutations alone. “In these cases, the tumor driving force might be less about mutations and more about different expression and splicing patterns,” Odenthal says. “There are some transcripts which are alternatively spliced and have a more oncogenic version of the protein.” Having this information can be relevant for decisions about which therapy to use, so Odenthal has been using a cohort of prostate cancer samples as the foundation for studies of DNA and RNA together. “QIAGEN has good chemistry to see the DNA mutations and in parallel to look at splicing variants and expression,” she notes.
In this pipeline, she combines DNA and cDNA in a single sequencing run. “You do the mutation and expression analysis in one workflow and you have everything together. I think modern pathology has to have everything in one pipeline,” Odenthal says. She believes that running separate FISH, NGS, and DNA promoter methylation analysis workflows will not be sustainable as diagnostic labs continue to ramp up their capacity. “It is much more efficient to have one workflow and get all this information,” she adds.
To learn more about how Dr. Odenthal has used QIAGEN Bioinformatics tools, read the full case study here.
Photo credit: Uniklinik Köln