Interrogating Tumor Structural Variation and Nongenic Dark Matter with Whole-Transcriptome Profiling

The transcriptional expression of tumor genomes is exceptionally complex and often driven by extensive structural variation. Key oncogenic drivers can result from gene fusions of proto-oncogenes with novel fusion partners that can be difficult to detect by DNA sequencing alone, making RNA-seq an essential step in somatic tumor profiling approaches. More recently, expressed nongenic “dark matter” in tumors has also been hypothesized as a rich source of cancer neoantigens that may direct antitumor responses. However, a current challenge in enabling routine tumor RNA-seq is the standard use of formalin-fixed paraffin-embedded (FFPE) tissue preservation that causes damage to RNA molecules and can result in poor sequencing quality.

In this webinar, Brian Piening, Technical Director of clinical genomics at the Providence Molecular Genomics Lab, will describe approaches for unbiased whole-transcriptome profiling in FFPE tissues and describe some key applications of this technology for answering novel questions in cancer biology.

This webinar will cover:

• Lessons learned from the implementation of an FFPE RNA sequencing pipeline
• Challenges in RNA sequencing with FFPE samples and methods for overcoming those challenges
• The value of whole-transcriptome sequencing for characterizing fusions
• RNA sequencing of tumor dark matter and validation with mass spectrometry-based proteomics
• Key considerations when implementing clinical RNA sequencing pipelines