Centrosome amplification arises before neoplasia and increases upon p53 loss in tumorigenesis.

摘要: Centrosome abnormalities are a typical hallmark of human cancers. However, the origin and dynamics such in cancer not known. In this study, we examined centrosomes Barrett’s esophagus tumorigenesis, well-characterized multistep pathway progression, from premalignant condition to metastatic disease. This model allows study sequential steps progression within same patient has representative cell lines all stages Remarkably, centrosome amplification was detected as early significantly expanded dysplasia. It then present throughout malignant transformation both adenocarcinoma metastasis. The expansion correlated with dependent on loss function tumor suppressor p53 through wild-type expression hotspot mutations. Our work shows that tumorigenesis can occur before transformation, being repressed by p53. These findings suggest humans contribute initiation progression.