Loss of TET reprograms Wnt signaling through impaired demethylation to promote lung cancer development.

ABSTRACT: Oncogenic imbalance of DNA methylation is well recognized in cancer development. The ten-eleven translocation (TET) family of dioxygenases, which facilitates DNA demethylation, is frequently dysregulated in cancers. How such dysregulation contributes to tumorigenesis remains poorly understood, especially in solid tumors which present infrequent mutational incidence of TET genes. Here, we identify loss-of-function mutations of TET in 7.4% of human lung adenocarcinoma (LUAD), which frequently co-occur with oncogenic KRAS mutations, and this co-occurrence is predictive of poor survival in LUAD patients. Using an autochthonous mouse model of Kras^G12D -driven LUAD, we show that individual or combinational loss of Tet genes markedly promotes tumor de

SUBMITTER: Xu Q 

PROVIDER: S-EPMC8832965 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature