Epigenetic MLH1 silencing concurs with mismatch repair deficiency in sporadic, naturally occurring colorectal cancer in rhesus macaques.
Simon DeycmarBrendan J JohnsonKarina RayGeorge W SchaafDeclan Patrick RyanCassandra CullinBrandy L DozierBetsy FergusonBenjamin N BimberJohn D OlsonDavid L CaudellChristopher T WhitlowKiran Kumar Solingapuram SaiEmily C RomeroFrancois J VillingerArmando G BurgosHannah C AinsworthLance D MillerGregory A HawkinsJeff W ChouBruno GomesMichael HettichMaurizio CeppiJehad CharoJ Mark ClinePublished in: Journal of translational medicine (2024)
These data indicate that epigenetic silencing suppresses MLH1 transcription, induces the loss of MLH1 protein, abrogates mismatch repair, and drives genomic instability in naturally occurring CRC in rhesus macaques. We consider this spontaneous, uninduced CRC in immunocompetent, treatment-naïve rhesus macaques to be a uniquely informative model for human CRC.
Keyphrases
- dna methylation
- gene expression
- endothelial cells
- signaling pathway
- late onset
- replacement therapy
- electronic health record
- transcription factor
- copy number
- protein protein
- induced pluripotent stem cells
- big data
- pluripotent stem cells
- small molecule
- machine learning
- combination therapy
- genome wide
- deep learning
- smoking cessation