Telomerase reactivation induces progression of mouse Braf ^V600E -driven thyroid cancers without telomere lengthening.

ABSTRACT: Mutations in the promoter of the telomerase reverse transcriptase ( TERT ) gene are the paradigm of a cross-cancer alteration in a non-coding region. TERT promoter mutations (TPMs) are biomarkers of poor prognosis in several tumors, including thyroid cancers. TPMs enhance TERT transcription, which is otherwise silenced in adult tissues, thus reactivating a bona fide oncoprotein. To study TERT deregulation and its downstream consequences, we generated a Tert mutant promoter mouse model via CRISPR/Cas9 engineering of the murine equivalent locus (Tert ^-123C>T ) and crossed it with thyroid-specific Braf ^V600E -mutant mice. We also employed an alternative model of Tert overexpression (K5-Tert). Whereas all Braf ^V

SUBMITTER: Landa I 

PROVIDER: S-EPMC9900760 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature