ETV1-Positive Cells Give Rise to BRAF^V600E -Mutant Gastrointestinal Stromal Tumors.

ABSTRACT: Gastrointestinal stromal tumor (GIST) is the most common subtype of sarcoma. Despite clinical advances in the treatment of KIT/PDGFRA-mutant GIST, similar progress against KIT/PDGFRA wild-type GIST, including mutant BRAF-driven tumors, has been limited by a lack of model systems. ETV1 is a master regulator in the intestinal cells of Cajal (ICC), thought to be the cells of origin of GIST. Here, we present a model in which the ETV1 promoter is used to specifically and inducibly drive Cre recombinase in ICC as a strategy to study GIST pathogenesis. Using a conditional allele for Braf^V600E , a mutation observed in clinical cases of GIST, we observed that Braf^V600E activation was sufficient to drive ICC hyperplasia but not GIST tumorigenesis. In

SUBMITTER: Ran L 

PROVIDER: S-EPMC5513719 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature