BRAF^V600E drives dedifferentiation in small intestinal and colonic organoids and cooperates with mutant p53 and Apc loss in transformation.

ABSTRACT: BRAF^V600E confers poor prognosis and is associated with a distinct subtype of colorectal cancer (CRC). Little is known, however, about the genetic events driving the initiation and progression of BRAF^V600E mutant CRCs. Recent genetic analyses of CRCs indicate that BRAF^V600E often coexists with alterations in the WNT- and p53 pathways, but their cooperation remains ill-defined. Therefore, we systematically compared small and large intestinal organoids from mice harboring conditional Braf^floxV600E, Trp53^LSL-R172H, and/or Apc^flox/flox alleles. Using these isogenic models, we observe tissue-specific differences toward sudden BRAF^V600E expression, which can be attributed to different ERK-pathway ground states in small

SUBMITTER: Reischmann N 

PROVIDER: S-EPMC7498370 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature