Activating mutation
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Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. Acquired functional mutations in the tyrosine-protein kinase growth factor receptor proto-oncogene (KIT) and platelet-derived growth factor-alpha gene lead to increased tyrosine kinase activity, which is considered a key factor in the pathogenesis of GIST.
14p vikoch 27-06-2024 1 1 Download
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Pediatric low-grade glioma (pLGG) is essentially a single pathway disease, with most tumors driven by genomic alterations affecting the mitogen-activated protein kinase/ERK (MAPK) pathway, predominantly KIAA1549::BRAF fusions and BRAF V600E mutations. This makes pLGG an ideal candidate for MAPK pathway-targeted treatments.
11p vikoch 27-06-2024 1 1 Download
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Oxidoreductases (ORases) are enzymes that catalyze oxidation and reduction reactions in cells or extracellular compartments of the body. Genetic mutations and other factors that affect ORase activity have been implicated in a range of diseases, especially inherited metabolic disorders. Aldose reductase, sorbitol dehydrogenase, xanthine oxidoreductase are the ORases with relevance to diabetes pathology.
7p dianmotminh02 03-05-2024 3 1 Download
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Base substitution catalogues represent historical records of mutational processes that have been active in a cell. Such processes can be distinguished by various characteristics, like mutation type, sequence context, transcriptional and replicative strand bias, genomic distribution and association with (epi)-genomic features.
11p vibransone 28-03-2024 5 2 Download
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The Ras pathway genes KRAS, BRAF, or ERBBs have somatic mutations in ~ 60% of human colorectal carcinomas. At present, it is unknown whether the remaining cases lack mutations activating the Ras pathway or whether they have acquired mutations in genes hitherto unknown to belong to the pathway.
13p vibransone 28-03-2024 6 2 Download
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Knowing the activity of the mutational processes shaping a cancer genome may provide insight into tumorigenesis and personalized therapy. It is thus important to characterize the signatures of active mutational processes in patients from their patterns of single base substitutions.
12p vibransone 28-03-2024 9 2 Download
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Chemogenetic profiling enables the identification of gene mutations that enhance or suppress the activity of chemical compounds. This knowledge provides insights into drug mechanism of action, genetic vulnerabilities, and resistance mechanisms, all of which may help stratify patient populations and improve drug efficacy.
12p vibransone 28-03-2024 5 2 Download
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Next-generation sequencing (NGS) of cancer gene panels are widely applied to enable personalized cancer therapy and to identify novel oncogenic mutations. Methods: We performed targeted NGS on 932 clinical cases of non-small-cell lung cancers (NSCLCs) using the Ion AmpliSeq™ Cancer Hotspot panel v2 assay.
11p vioraclene 31-03-2024 3 2 Download
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Krüppel-type zinc finger genes (ZNF) constitute a large yet relatively poorly characterized gene family. ZNF genes encode proteins that recognize specific DNA motifs in gene promotors. They act as transcriptional co-activators or -repressors via interaction with chromatin remodeling proteins and other transcription factors.
10p vioraclene 31-03-2024 3 1 Download
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Genomic analysis of the molecular neuropathology of tuberous sclerosis using a human stem cell model
Tuberous sclerosis complex (TSC) is a genetic disease characterized by benign tumor growths in multiple organs and neurological symptoms induced by mTOR hyperfunction. Because the molecular pathology is highly complex and the etiology poorly understood, we employed a defined human neuronal model with a single mTOR activating mutation to dissect the disease-relevant molecular responses driving the neuropathology and suggest new targets for treatment.
14p vioraclene 31-03-2024 2 1 Download
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Basal cell carcinoma (BCC) of the skin is the most common form of human cancer, with more than 90% of tumours presenting with clear genetic activation of the Hedgehog pathway. However, polygenic risk factors affecting mechanisms such as DNA repair and cell cycle checkpoints or which modulate the tumour microenvironment or host immune system play significant roles in determining whether genetic mutations culminate in BCC development.
12p vibransone 28-03-2024 3 2 Download
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Genes with multiple co-active promoters appear common in brain, yet little is known about functional requirements for these potentially redundant genomic regulatory elements. SCN1A, which encodes the NaV1.1 sodium channel alpha subunit, is one such gene with two co-active promoters.
22p vibransone 28-03-2024 5 2 Download
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Hundreds of thousands of cancer patients have had targeted (panel) tumor sequencing to identify clinically meaningful mutations. In addition to improving patient outcomes, this activity has led to significant discoveries in basic and translational domains.
14p vibransone 28-03-2024 2 2 Download
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The mutational profile of cancer reflects the activity of the mutagenic processes which have been operative throughout the lineage of the cancer cell. These processes leave characteristic profiles of somatic mutations called mutational signatures. Mutational signatures, including single-base substitution (SBS) signatures, may reflect the effects of exogenous or endogenous exposures.
16p viellison 28-03-2024 6 2 Download
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The activation of the telomere maintenance mechanism (TMM) is one of the critical drivers of cancer cell immortality. In gliomas, TERT expression and TERT promoter mutation are considered to reliably indicate telom‑ erase activation, while ATRX mutation and/or loss indicates an alternative lengthening of telomeres (ALT). However, these relationships have not been extensively validated in tumor tissues.
16p viellison 28-03-2024 3 1 Download
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Germline variants affecting the proof reading activity of polymerases epsilon and delta cause a hereditary cancer and adenomatous polyposis syndrome characterized by tumors with a high mutational burden and a spe‑ cifc mutational spectrum.
18p vicwell 29-02-2024 4 2 Download
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Permanent neonatal diabetes mellitus (PNDM) presents with dehydration and hyperglycemia, which usually occurs during the frst 12 months of life. Activating mutations of beta-cell adenosine triphosphate-sensitive potassium [KATP] channel subunits that cause opening of the channel are associated with PNDM.
5p vilazada 31-01-2024 5 2 Download
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Ebook "Hepatitis B virus: Methods and protocols" details protocols and techniques ranging from cell culture studies to in vivo and clinical immunology. The chapters in this book discuss treatments of in vitro infection systems, analysis and quantification of cccDNA and its mutations; in vitro polymerase activity assays; cellular trafficking of core proteins; intracellular calcium metabolism; detection, cloning, and sequencing of HBV markers; and new strategies aimed at exploiting new mechanisms for drug discovery.
301p lucchinguyen 28-12-2023 5 2 Download
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Hepatocellular carcinoma (HCC) is a fatal disease characterized by early genetic alterations in telomerase reverse transcriptase promoter (TERTp) and β-catenin (CTNNB1) genes and immune cell activation in the tumor microenvironment. As a novel approach, we wanted to assess patient survival influenced by combined presence of mutations and densities of CD8+ cytotoxic T cells.
10p vialfrednobel 23-12-2023 4 3 Download
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Activated mutations in NOTCH1 are drivers of T-cell type acute lymphoblastic leukemia/lymphoma. The γ-secretase inhibitor (GSI), which suppresses the function of NOTCH1, is expected to be a molecular-targeted agent. NOTCH1 is also expressed in other malignant neoplasms.
7p vialfrednobel 23-12-2023 4 3 Download