Free MTAP Reviewers for Grade 9 (PDF Download) - DepEd Click
our observations may challenge the current dogma of the role of prmt5 in cancer. as we have shown, mtap deletion sensitizes cancer cells to prmt5 inhibitors. nonetheless, we stress that such generalization must be tempered with evidence that mtap deletion had co-operative effects with distinct oncogenic genetic events that were also present in certain tumors. for instance, prmt5 inhibition has been suggested to exhibit a co-operative effect with kras mutations in kras-mutant cancers 66 , and with homozygous deletion of cdkn2a/b or of loss of 9p21 copy number in gbm 2 . we clearly demonstrated the co-operative effects of mtap deletion with cdkn2a/b homozygous deletion in gbm, and therefore cautiously suggest that prmt5 inhibitors are also capable of overcoming this genetic complexity in some tumors. in support of this, intracellular mta levels in mtap-deleted u251 (glioblastoma) cells were substantially less in the presence of glioma-conditioned medium. in addition, our previous work showed that cdkn2a/b homozygous deletion is a strong predictor of adverse patient outcomes in patients with pancreatic carcinoma and other solid cancers. in gbm, the cdkn2a/b locus is homogeneously deleted in the majority of cases 7, 8 , but different types of genetic aberrations that co-operate with mtap-intact cells may only be observed in certain tumors. furthermore, it is possible that mtap-deleted cells would be invulnerable to prmt5 inhibitors in cases of other co-operating genetic events of relevance to gbm, whereas human cases of gbm with prmt5 inhibitors also show mtap-intact cells, regardless of genetic heterogeneity that may occur in some human tumors.
mtap grade 9 reviewer pdf download