Metabolic reprogramming by mutant GNAS creates an actionable dependency in intraductal papillary mucinous neoplasms of the pancreas.

ABSTRACT:

Background

Oncogenic 'hotspot' mutations of KRAS and GNAS are two major driver alterations in intraductal papillary mucinous neoplasms (IPMNs), which are bona fide precursors to pancreatic ductal adenocarcinoma. We previously reported that pancreas-specific Kras ^G12D and Gnas ^R201C co-expression in p48^Cre; Kras^LSL-G12D; Rosa26^LSL-rtTA; Tg (TetO-Gnas^R201C) mice ('Kras;Gnas' mice) caused development of cystic lesions recapitulating IPMNs.

Objective

We aim to unveil the consequences of mutant Gnas ^R201C expression on phenotype, transcriptomic profile and genomic dependencies.

Design

We performed multimodal transcriptional profiling (bulk RNA seque

SUBMITTER: Makino Y 

PROVIDER: S-EPMC12014225 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature