SMAD4 and neoplasm: Remarkably, in EAC, not only alterations of classical driver genes such as TP53, CDKN2A, SMARCA4, ARID1A, SMAD4, ERBB2 or PIK3CA but also those of helper genes such as ABI2 and NCOR2, which are mutated only at a low frequency in single patients, contribute to tumor development [17,65,66].