Divergent PTEN-p53 interaction upon DNA damage in a human thyroid organoid model with germline PTEN mutations.

ABSTRACT: Germline mutations in the tumor suppressor phosphatase and tensin homolog (PTEN) cause PTEN hamartoma tumor syndrome (PHTS). PHTS is characterized by an elevated lifetime risk of differentiated thyroid cancer (DTC), 30 times higher than the general population. However, only 1 in 3 PHTS patients develop DTC, and it remains unknown whether specific PTEN variants are associated with an increased risk of DTC. PTEN antagonizes the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway, a frequently affected pathway in sporadic DTC. PTEN also acts as a guardian of the genome by interacting with other tumor suppressors. Here, we report how ionizing radiation, an environmental tumorigenic contributor, modifies the DNA damage response based on the type of germline PTEN variants. We hypothesized

SUBMITTER: Venegas JA 

PROVIDER: S-EPMC11906015 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature