The large number of sequencing data revealed several new significantly mutated genes in ESCC, including PPFIA2, TGFBR2, ZBBX, ATP13A5 and IRF2BPL. In addition, novel recurrent frameshift deletions in TGFBR2 and IRF2BPL were identified, indicative of their tumor suppressing functions. Here, TGFBR2 is linked to esophageal squamous cell carcinoma.