Whole exome sequencing of pancreatic cancer metastases and matched primary tumors

Pancreatic ductal adenocarcinoma (PDAC) is among the most deadly malignancies due to late diagnosis, frequent chemoresistance, and rapid metastasizing. Little is known about the molecular background of the metastatic process, while the location of the metastasis may carry prognostic information and potentially therapeutic opportunities. We aimed to explore genomic profiles of PDAC metastases from diverse loci and their value for the patients' therapeutic management. DNA samples from paired primary and metastatic tissue of 20 patients were microdissected and sequenced using whole exome target enrichment. KRAS, TP53, SMAD4, and CDKN2A were the most commonly mutated oncodrivers in primary tumors and metastases. Patients with mutated KRAS, high mutational load, and frequent CNVs in metastatic loci had shortened survival after metastasis resection. The observed associations encourage further molecular profiling for personalized treatment of PDAC patients with different metastasis localization scenarios.