EP-300

PIK3CA, RB1, FGFR3, KMT2C, MACF1, RYR2, and EP300 are differentially mutated among three immunotypes...Low expression of ACTA2 was associated with the MIBC survival benefit. The current study constructs a model that could identify suitable MIBC patients for immunotherapy, and it is an important step forward to the personalized treatment of bladder cancers.

In addition, a disruption in this chromosomal interaction prevented the histone acetyltransferase EP300 from embedding in the promoter of NTS and resulted in NTS silencing. Most importantly, in vitro and in vivo experiments showed that the ability of tumor formation was significantly suppressed via deletion of the enhancer by CRISPR-Cas9. These studies delineate a novel onco-enhancer guided epigenetic mechanism and provide a promising therapeutic concept for disease therapy.

In detail, we defined EP300 as a panCancer inhibitor of the TIME most likely via metabolic modulation. In this context EP300 represents a promising predictive biomarker and an immuno-therapeutic target.

Tamoxifen (TAM) was applied to evaluate the influence of TRIM27 on chemoresistance of breast cancer cells, while co-immunoprecipitation (coIP) was performed to identify the E3 ubiquitin ligase capability of TRIM27...In addition, EP300 could enhance the expression of TRIM27 and its transcription promoter H3K27ac. TRIM27, through ubiquitination of p21, might serve as a prognostic biomarker for non-TNBC prognosis. TRIM27 functions as a novel oncogene in non-TNBC cellular processes, especially suppressing cell senescence and interfering with non-TNBC chemoresistance.

Different high frequency gene mutations could be found between the patients with high and negative PDL1. PDL1 expression combined with specific gene mutation may better predict the survival for patients receiving atezolizumab.

The novel signaling axis circSOD2/miR-502-5p/DNMT3a/JAK2/STAT3/circSOD2 provides a better understanding of HCC tumorigenesis. The molecular mechanism underlying this signaling axis offers new prevention and treatment of HCC.

The upregulation of GPNCA was partly due to enhanced H3K27ac occupancy on its promoter region via EP300 and KAT2A/GCN5...Our in vitro experiments demonstrated that GPNCA silencing inhibited tumor growth via inhibiting its nearby gene GSK3B. Taken together, these findings highlight GPNCA as a biomarker for cancer diagnosis and a potential target for future cancer drug development.

Relative to EA TNBC, AA TNBC tumors exhibited higher mutation rates in TP53 (94% vs 86%), KMT2C (17% vs 9%), APOB (19% vs 10%), BRCA2 (11% vs 5%), EP300 (8% vs 2%), NOTCH1 (12% vs 4%), and EGFR (11% vs 4%)... These data demonstrate significant differences in breast tumor heterogeneity and mutation spectrum in TNBC and HR+/HER2- breast cancers between AA and EA patients. Ancestral differences were also observed in the activity of relevant signaling pathways for TNBC. Overall, the results identify previously unexplored pathways and molecular phenotypes of aggressive disease, providing opportunities for development of more effective biomarker informed treatment of breast cancer in diverse populations.

Eight genes, including DDX58 (RIG-I), BAX, EP300, and SPP1 (osteopontin), contained mutations observed only in Huh7.5.1-8 or mutations with higher frequency in Huh7.5.1-8. These mutations might be relevant to phenotypic differences between the two cell lines and may also serve as genetic markers to distinguish Huh7.5.1-8 cells from the ancestral HuH-7 cells.

Very similar to previously described, top ten mutated genes were: CREBBP (75%), KMT2D (73%), BCL2 (46%), TNFRSF14 (43%), EZH2 (23%), STAT6 (21%), EP300 (19%), MEF2B (19%), IGLL5 (18%) and ARID1A (17%). Of note, we found that there is one third of FL patients that present with mutations in genes affecting the mTORC1 pathway, showing poor outcomes when treated with R-CVP/R-CHOP but not if treated with R-B. Evaluation of mTORC1 targeted therapies might be of interest in this subset of FL.

Ex vivo drug treatments included: BCL2i (inhibitor): venetoclax; MCL-1i: AZD5991, S63845 and BCLXLi: A133...No mutations in EZH2, CREBBP or EP300 were found... The genomic landscape of BCL2-R CLL is characterized by a high frequency of trisomy 12, subclonal NOTCH and RAS pathway mutations, as well as BCL2 and MLL2 mutations. Protein expression, BH3 profiling and viability assays data are consistent with nearly exclusive dependence on Bcl-2. Our data suggest that Bcl-2 inhibition should be favored over Mcl-1 inhibition in BCL2-R CLL.