Factors targeting MED12 to drive tumorigenesis

摘要: Mediator Complex Subunit 12 (MED12) is part of the transcriptional preinitiation machinery. Mutations its gene predominantly occur in two types highly frequent benign tumors, uterine leiomyomas and fibroadenomas breast, where they apparently act as driver mutations. Nevertheless, their presence not restricted to tumors having been found at considerable frequencies leiomyosarcomas, malignant phyllodes chronic lymphocytic leukemia also. Most mutations are located within exon 2 but rare cases intron 1/exon boundary or 1 affected. As type, single nucleotide exchanges with a hotspot one codon found, small deletions clustering around that also uncommon. These latter leaving open reading frame intact. mutations, so far no apparent differences between tumor entities affected have emerged. Interestingly, this pattern clustered resembles seen result targeted editing. In contrast other percentage MED12 -mutation positive independent clonal origin increases number per patient suggesting unknown etiological factors supporting site specific mutagenesis.  These may by inducing simultaneous site-specific double strand breaks erroneous repair which lead corresponding inducers DNA damage such foreign nucleic acids microbiome displaying sequence homology putative target might play role. 16 base pair terminator base-paired hairpin Staphylococcus aureus tRNA cluster has noted form R-loop like structures thus said changes.