A paper just published in Nature Communications describes a molecular analysis of Pancreatic Cancer by tumour exome and ctDNA targeted sequencing. The results showed enrichment of mutations in known PaCa associated genes, and identified clinically actionable mutations in over 1/3rd of patients.
Marc Sausen in Victor Velculescu's lab at Johns Hopkins analysed 101 patients with Pancreatic cancer using a deep sequencing approach via exome and ctDNA analysis of 115 genes. To maximise tumour content samples were either macro-dissected, or (if that was hard enough) anueploid nuclei were flow sorted after disaggregation. They generated 230x exome and 750x amplicon sequencing.
The three most exciting bits for me were firstly that over a third of the patients had clinically actionable mutations associated with an approved therapy, a therapy in a published clinical trial or a therapy in an ongoing clinical trial. This list included ERBB2 amplification potentially treatable by Herceptin and also reported in a previous ICGC study.
Secondly, that these methods open the possibility of detecting PaCa in asymptomatic patients by focusing on a few specific PaCa mutation. They referenced CAPP-seq for NSCLC, which used a 521 exons and 13 introns panel covering 139 recurrently mutated genes, covering only 125 kb; combined with very deep sequencing to around 10,000 fold coverage. et al's
Thirdly they did not use RNA-seq but SAGE for differential gene expression analyses.