Project description:Interventions: IHC of MMR proteins, genetic or epigenetic analyses of MMR genes
Primary outcome(s): Screening of HNPCC related tumors by IHC for loss of MMR protein expression and observation of the clinical features assciated with MMR deficiency.
Study Design: Single arm Non-randomized
Project description:Leukemia is characterized by genetic and epigenetic mutations resulting in selection of cancer stem cells, which are unable to differentiate. While genetic alterations are difficult to target, the epigenome is intrinsically dynamic and readily offers new therapeutic strategies. Thus, identifying cancer-specific context-dependent targets and unraveling their biological function may open up new therapeutic perspectives. Here, we identify bromodomain-containing protein 9 (BRD9) as a critical target required in acute myeloid leukemia (AML). We show that BRD9 is overexpressed in AML cells including ex vivo primary blasts compared to CD34+. By targeting BRD9 expression in AML, we observed an alteration in proliferation and survival, ultimately resulting in the induction of apoptosis. Intriguingly, genome-wide profiling revealed that BRD9 binds enhancer regions in a cell type-specific manner, regulating cell type-related processes. We unveil a novel BRD9-sustained STAT5 pathway activation via regulation of SOC3 expression levels. Our findings identify a previously undescribed BRD9-STAT5 axis as critical for leukemia maintenance, suggesting BRD9 as a potential therapeutic target.
Project description:Genetic variation governs protein expression through both transcriptional and post-transcriptional processes. To investigate this relationship, we combined a multiplexed, mass spectrometry-based method for protein quantification with an emerging mouse model harboring extensive genetic variation from 8 founder strains. We collected genome-wide mRNA and protein profiling measurements to link genetic variation to protein expression differences in livers from 192 diversity outcross mice. We observed nearly 3,700 protein-level quantitative trait loci (pQTL) with an equal proportion of proteins regulated directly by their cognate mRNA as uncoupled from their transcript. Our analysis reveals an extensive array of at least five models for genetic variant control of protein abundance including direct protein-to-protein associations that act to achieve stoichiometric balance of functionally related enzymes and subunits of multimeric complexes.
Project description:This SuperSeries is composed of the following subset Series: GSE34906: Genetic and epigenetic determinants of neurogenesis and myogenesis [ChIP-seq] GSE34907: Genetic and epigenetic determinants of neurogenesis and myogenesis [expression profiling] Refer to individual Series
Project description:Primary outcome(s): Correlation between image evaluation/clinical data and molecular predictive and/or prognostic factors including genetic and epigenetic alterations derived from colorectal cancer tissues
| 2631489 | ecrin-mdr-crc
Project description:Genetic and Epigenetic Profiling of the Infertile Male
Project description:The goal of this laboratory research is to look for genetic and epigenetic markers that can predict which patients with stage III colorectal cancer will benefit from fluorouracil-based adjuvant chemotherapy.
Project description:The next generation of personalized medical treatment according to the type of personal genetic information are evolving rapidly. The genome analysis needs systematic infra and database based on personal genetic information. Therefore, a big data of genome-clinical information is important.
To determine the feasibility of the use of tumor’s molecular profiling and targeted therapies in the treatment of advanced cancer and to determine the clinical outcome(Response rate,PFS, duration of response and overall survival )of patients with advanced cancer, the investigators are going to take a tumor tissue of patients and process molecular profiling and receive molecular profile directed treatments.