In the larger cohort of tissue samples, the genes overlapping between colon and rectal cancer among the top 10 genes with highest alteration frequency were located in relevant signaling pathways, including the Wnt pathway (APC), RAS and PI3K pathways (KRAS, PIK3CA), TGFB (SMAD4), and NOTCH signaling pathway (SOX9), in addition to tumor suppressor genes such as TP53 and FBXW7 (Fig. S2A,C). The gene discussed is SMAD4; the disease is rectal cancer.