The Use of Integrated Whole-genome DNA and RNA Sequencing Analysis for Understanding of Individual Cancer Cases

The use of genomic sequencing in individual cancer care offers the promise of treatments suited to the specific characteristics of a patient's disease.  Here, we survey the combined use of RNA and DNA analysis for cancer management.  While DNA sequencing of tumors can identify the primary lesions responsible for the cancerous state, RNA sequencing enriches the information in ways that both complement and extend the information provided by DNA alone.  Among the uses of RNA sequencing in the context of whole-genome sequencing are: 1) verifying the presence of mutations identified in the DNA sequence through an orthogonal assay; 2) discovering gene fusions, which are more difficult to identify in the much more complex genomic DNA background; 3) confirming that the mutant transcript is expressed, appropriately spliced, and in frame (or not, in cases where the mutation disrupts expression, splicing, or reading frame); 4) identifying treatment-relevant biological states through expression signatures; (5) confirming the pathway effects of mutations.