TP53 and Barrett esophagus: Meanwhile, Stachler et al.14 noted that there might be two paths for BE to transform to EAC: one way is through a gradual loss of tumor suppressor genes followed by genomic instability and amplification of oncogenes; the other way starts with the inactivation of TP53, followed by whole-genome doubling, which facilitates genomic instability and oncogene activation.