Interestingly, while spasmolytic polypeptide-expressing metaplasia (SPEM), another putative precursor to gastric adenocarcinoma, was suggested to be not associated with Lgr5(+) cells in the variegated Lgr5-EGFP-IRES-Cre (ERT2/+); in Rosa26R mice [31], expression of constitutively active Kras (harboring p.G12D hotspot mutation) in Lgr5(+) chief cells was sufficient form SPEM in a non-variegated Lgr5-2A-CreERT2 mouse model [10]. Here, MAPK3 is linked to gastric adenocarcinoma.