These results suggest that Ezh2(Y641F) induces lymphoma and melanoma through a vast reorganization of chromatin structure, inducing both repression and activation of polycomb-regulated loci.
As EZH2 mutations often coincide with other mutations in lymphoma, we combined the expression of EZH2(Y641F) by crossing these transgenic mice with Eµ-Myc transgenic mice.
Among the three polymorphic sites examined, the genotypes of EZH2 rs887569 (C to T), but not rs41277434 (A to C) or rs3757441 (T to C), were positively associated with bladder cancer risk (p for trend =0.0146).
Among the three polymorphic sites examined, the genotypes of EZH2 rs887569 (C to T), but not rs41277434 (A to C) or rs3757441 (T to C), were positively associated with bladder cancer risk (p for trend =0.0146).
Our findings provide evidence that the T allele of EZH2 rs887569 may be associated with the lower risk of bladder cancer development, especially among non-smokers.
In addition, we demonstrated that decreased GATA3 levels are required for progestin-induced upregulation of cyclin A2, which mediates the G1 to S phase transition of the cell cycle and was reported to be associated with poor prognosis in breast cancer.
Interestingly, mutation of EZH2 WT alone generated an intermediate resistance phenotype, which is consistent with a previously proposed model of cooperation between EZH2 WT and Y641N mutants to promote tumorigenesis.
Among the three polymorphic sites examined, the genotypes of EZH2 rs887569 (C to T), but not rs41277434 (A to C) or rs3757441 (T to C), were positively associated with bladder cancer risk (p for trend =0.0146).
Among the three polymorphic sites examined, the genotypes of EZH2 rs887569 (C to T), but not rs41277434 (A to C) or rs3757441 (T to C), were positively associated with bladder cancer risk (p for trend =0.0146).
Our findings provide evidence that the T allele of EZH2 rs887569 may be associated with the lower risk of bladder cancer development, especially among non-smokers.
Two polymorphisms of EZH2, rs6950683 and rs3757441, showed a statistically significant association with reduced risk of lung cancer (adjusted OR [aOR] = 0.71, p = 0.007; aOR = 0.73, p = 0.015, respectively).
Two polymorphisms of EZH2, rs6950683 and rs3757441, showed a statistically significant association with reduced risk of lung cancer (adjusted OR [aOR] = 0.71, p = 0.007; aOR = 0.73, p = 0.015, respectively).
As EZH2 mutations often coincide with other mutations in lymphoma, we combined the expression of EZH2(Y641F) by crossing these transgenic mice with Eµ-Myc transgenic mice.
These results suggest that Ezh2(Y641F) induces lymphoma and melanoma through a vast reorganization of chromatin structure, inducing both repression and activation of polycomb-regulated loci.
EZH2 rs3757441 C/C genotype is associated with stronger EZH2 and H3K27me3 immunoreactivity in primary CRC: this SNP may serve as a promising biomarker for EZH2-targeting agents and may add independent information to KRAS and BRAF testing.