The evolutionary history of metastatic pancreatic neuroendocrine tumors reveals a therapy driven route to high-grade transformation

#4103

Introduction: Tumor evolution with acquisition of more aggressive disease characteristics is a hallmark of disseminated cancer. Metastatic pancreatic neuroendocrine tumors (PanNETs) in particular, show frequent progression from a low/intermediate to a high-grade disease.

Aim(s): To understand the molecular mechanisms underlying metastatic progression as well as transformation from a low/intermediate to a high-grade PanNET.

Materials and methods: We performed multi-omics analysis (genome/exome sequencing, total RNA-sequencing and methylation array) of 32 longitudinal samples from six patients with metastatic low/intermediate grade PanNET. Findings were validated in post-alkylating chemotherapy samples from 24 PanNET patients using targeted next generation sequencing.

Conference:

Presenting Author: Crona J

Authors: Backman S, Botling J, Nord H, Ghosal S, Stålberg P,

Keywords: Pancreatic neuroendocrine tumor, Tumor evolution, Alkylating chemotherapy, Treatment resistance,