These molecular changes include (1) gene repression (deletion and loss of function mutations or transcriptional downregulation) such as lkb1 and pten in gastrointestinal hamartomatous polyposis syndromes (Boland et al., 2022), or prkci/z in aggressive colorectal cancers (Nakanishi et al., 2018), or (2) gene overexpression (from gene amplification or transcriptional upregulation), such as lgl2 in breast cancer positive for estrogen receptors (Saito et al., 2019). Here, ESR1 is linked to breast cancer.