Co‐altered tumors displayed frequent alterations in chromatin remodeling genes (CREBBP, ARID1A, and KMT2D) and PI3K pathway (PIK3CA and PTEN), but with distinct tissue‐specific mutational patterns: EGFR mutations dominated in lung adenocarcinoma (52%), KRAS in pancreatic cancer (88%), and APC in colorectal cancer (77%). Here, KMT2D is linked to familial pancreatic carcinoma.