In addition, five out of nine mutations identified in NOTCH2/3 were truncating, and two stopgains were identified in RBPJ, one of the target genes of NOTCH. Thus, in contrast to T-cell acute lymphoblastic leukemia, chronic lymphoblastic leukemia and breast cancer, in which NOTCH1 serves as an oncogene [31], this pattern of mutations suggest that the NOTCH pathway has a tumor suppressing role in ESCC. The gene discussed is NOTCH2; the disease is esophageal squamous cell carcinoma.