TRIM28
Overview
TRIM28 (Tripartite Motif Containing 28), also known as KAP1 or TIF1-beta, is a transcriptional co-repressor that recruits chromatin-remodeling complexes to silence gene expression. It interacts with KRAB-domain zinc finger proteins and plays roles in DNA damage response, stem cell pluripotency, and heterochromatin maintenance. In cancer, TRIM28 has been linked to the AMPK/mTOR signaling axis. TCGA pan-glioma analysis identified somatic TRIM28 promoter mutations that correlate with TRIM28 upregulation, nominating a mechanistic link to mTOR activation.
Alterations observed in the corpus
- TRIM28 promoter mutations (n=8) identified in diffuse glioma by TCGA pan-glioma WGS analysis; promoter mutation correlates with TRIM28 upregulation; mechanistic link to AMPK degradation and mTOR activation noted as candidate therapeutic axis for metformin sensitization PMID:26824661
Cancer types (linked)
- Diffuse glioma (LGG/GBM): recurrent TRIM28 promoter mutations identified in the TCGA pan-glioma cohort; TRIM28 upregulation associated with mTOR pathway activation PMID:26824661
Co-occurrence and mutual exclusivity
- TRIM28 promoter mutations occur in IDH-mutant and IDH-wildtype glioma contexts; specific co-mutation patterns not detailed in the corpus PMID:26824661
Therapeutic relevance
- TRIM28-promoter-mutant gliomas nominated as a setting where metformin or AMPK agonists may have heightened activity, based on TRIM28’s role in AMPK degradation (extrapolated from Pineda et al. 2015; not tested in this study) PMID:26824661
Open questions
- Therapeutic sensitivity of TRIM28-promoter-mutant glioma to metformin or AMPK agonists is inferential and has not been tested in patients or glioma models PMID:26824661
Sources
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