Profiling of epithelial and stromal cells in early proximal colon preneoplasia with matched normals.

Progression of nonmalignant colonic cells harboring somatic mutations depends upon interactions with surrounding stroma; however, details of this interaction are poorly understood. We performed targeted transcriptional profiling of laser-captured epithelial and stromal cells from ACF, the earliest detectable human colonic pre-neoplastic lesion. Within ACF epithelium carrying non-overlapping mutations in KRAS, BRAF, or APC, we observed broad NF-kB-related inflammatory changes and specific differences associated with each mutation, including BRAFV600E-mediated senescence. Additionally, we identified ACF-associated stromal changes indicative of immune cell infiltration and fibroblast activation. Our results provide new insight into intercellular signaling changes that control the earliest stages of CRC development.Â