Systematic integration of somatic mutation profiles and CNVs patterns through pathway enrichment analyses reveal that ESCC progression is orchestrated by dysregulation of six core signaling networks: (1) RTK-Ras-PI3K cascades, (2) JAK-STAT signaling, (3) Akt survival pathways, (4) NOTCH/Wnt developmental circuits, (5) cell cycle checkpoints, and (6) p53 tumor suppressor axis [8–13]. Here, AKT1 is linked to esophageal squamous cell carcinoma.