Multi-omics whole-genome characterization of the copy number landscape of metastatic pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with limited therapeutic options. While genome profiling has benefitted clinical decision-making in many cancer types, PDAC remains among the most lethal solid cancers and has relatively few clinically actionable molecular targets. Using a multi-omics approach, we integrate whole-genome and transcriptome datasets along with proteomics and clinical metadata to identify copy-altered regions with significant impact on expression at the whole-genome scale. This approach identified SMURF1, ARPC1A, ZSCAN25, and BRI3 as focally amplified and over-expressed genes located on chr7q21/22 with expression negatively correlated with patient survival. We extrapolate these results into a pan-cancer analysis to demonstrate that the association between SMURF1 amplification versus expression is strongest in PDAC among 23 other cancer types. Taken together, these data provide a detailed overview of the copy number landscape in PDAC while highlighting chr7q21/22 amplification as a recurrent somatic event impacting both gene expression and patient survival.