For example, SMAD4 mutations expanded during metastasis in GB-A1 and GB-S3 (Figure 2A and D) and have been associated with distant metastasis and poor prognosis in various cancers, including GBAC (Narayan et al., 2019; Jamal-Hanjani et al., 2017; Yoon et al., 2021; Zhao et al., 2018). This evidence concerns the gene SMAD4 and cancer.