Bacterial-Driven Inflammation and Mutant <i>BRAF</i> Expression Combine to Promote Murine Colon Tumorigenesis That Is Sensitive to Immune Checkpoint Therapy.

ABSTRACT: Colorectal cancer is multifaceted, with subtypes defined by genetic, histologic, and immunologic features that are potentially influenced by inflammation, mutagens, and/or microbiota. Colorectal cancers with activating mutations in BRAF are associated with distinct clinical characteristics, although the pathogenesis is not well understood. The Wnt-driven multiple intestinal neoplasia (Min^ApcΔ716/+) enterotoxigenic Bacteroides fragilis (ETBF) murine model is characterized by IL17-dependent, distal colon adenomas. Herein, we report that the addition of the BRAF ^V600E mutation to this model results in the emergence of a distinct locus of midcolon tumors. In ETBF-colonized BRAF ^V600E Lgr5 ^CreMin (BLM) mice, tumors h

SUBMITTER: DeStefano Shields CE 

PROVIDER: S-EPMC8295175 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature