Target genes novel gene fusion oncogenic oncogene fusion. Medical search. Frequent questions

In addition, these alterations affect 3 principal categories of genes, as follows: proto-oncogenes, tumor suppressor genes, and DNA repair genes. (medscape.com)
This article briefly discusses tumor suppressor genes and then focuses on the role of proto-oncogenes in childhood cancer. (medscape.com)
Driver events in pediatric malignancies can occur through loss of function in tumor suppressor genes or gain of function in proto-oncogenes. (medscape.com)
Recurrent mutations in proto-oncogenes comprise a large proportion of therapeutically targetable alterations in lung cancer. (gotoper.com)

We have tested it on matched RNA-Seq and WGS data for both tumors and cancer cell lines and show that it can be used to validate both new predicted gene fusions and experimentally validated fusion events. (biomedcentral.com)
[ 2 ] Targeted disruption of TP53 in the mouse leads to the development of various tumors (see image below). (medscape.com)
Although carcinogenic roles for the INK4B, INK4C, INK4D, CIP1, KIP1, and KIP2 genes appear to be limited, INK4A is among the most commonly mutated genes in human tumors. (medscape.com)
FOs are ideal therapeutic targets for the development of new directed cancer treatments, owing to their cancer-driving roles, their restriction to cancer cells and the reliance of tumors on them. (skincare.nz)
Moreover, the potential of off-label prescription of targeted therapies favors classifying tumors based on DNA alterations rather than traditional tissue pathology. (oncotarget.com)
The BRAF V600E mutation is an important oncological target in certain central nervous system (CNS) tumors, for which a possible application of BRAF-targeted therapy grows continuously. (hindawi.com)
We used integrative three-dimensional (3D) spatial genomics to identify the chromatin interaction targets of 45 prostate cancer risk alleles, 31 of which were associated with the transcriptional regulation of target genes in 565 localized prostate tumors. (stanford.edu)
To supplement these 31, we verified transcriptional targets for 56 additional risk alleles using linear proximity and linkage disequilibrium analysis in localized prostate tumors. (stanford.edu)
Gene fusion is found to be significantly increased in cerebellar pilocytic astrocytoma tumors. (springeropen.com)
This is mainly attributed to cellular heterogeneity of these tumors with multiple cell of origin, lack of effective drugs that cross the blood brain barrier and the absence of molecular markers that could be used for targeted therapy. (springeropen.com)
Herein, we wondered whether circular RNAs (circRNAs), a type of RNA transcripts lacking 5′-3′ ends and forming closed loops that are gaining relevance in cancer biology, are also a target of epigenetic inactivation in tumors. (oncotarget.com)
Additional screens for MMTV provirus entry sites in tumors revealed several other upregulated genes that are associated with other gene development pathways such as INT2, INT3, and INT4 [4,5,6]. (chemdiv.com)

The Cancer Gene Census (CGC) is an ongoing effort to catalogue those genes which contain mutations that have been causally implicated in cancer and explain how dysfunction of these genes drives cancer. (sanger.ac.uk)
To be classified into Tier 1, a gene must possess a documented activity relevant to cancer, along with evidence of mutations in cancer which change the activity of the gene product in a way that promotes oncogenic transformation. (sanger.ac.uk)
For instance, tumour suppressor genes often show a broad range of inactivating mutations and dominant oncogenes usually demonstrate well defined hotspots of missense mutations. (sanger.ac.uk)
The gene list has been annotated with information concerning chromosomal location, tumour types in which mutations are found, classes of mutation that contribute to oncogenesis and other genetic properties. (sanger.ac.uk)
We are also developing new therapeutic approaches to correct non-sense mutations that account for 5-40% of mutations affecting tumour suppressor genes and are responsible for about 10% of genetic diseases. (pluginlabs-hautsdefrance.fr)
Genetic drivers are mutations or fusions that confer a survival advantage to "drive" malignant proliferation. (medscape.com)
[ 3 ] Loss of function mutations in this gene are implicated in pediatric retinoblastoma. (medscape.com)
Furthermore, cfDNA sequencing resulted in increased identification of potentially actionable mutations compared with tissue-based NGS, including clinically relevant mutations in the BRAF , FGFR2 , and EGFR oncogenes, the last of which was associated with durable clinical benefit in a patient treated with the EGFR inhibitor erlotinib. (aacrjournals.org)
This mini-review will focus on the current knowledge of FGFR mutations, which lead to tumor formation and summarizes the state-of-the-art therapeutic strategies for targeted treatments against the FGFRs/FGFs axis in the context of BC. (123dok.org)
Molecular diagnostic algorithms have undergone a significant evolution over time, moving from a 'one-gene, one-test' paradigm to the inclusion of multiplex assays for common hotspot point mutations, and insertions and deletions. (gotoper.com)
While current testing in most centers is charac-terized by a combination of several different single-gene or multiplex diagnostic assays, the advent of next-generation sequencing has provided a means of interrogating mutations, rearrangements, and copy number changes across a variety of therapeutically relevant oncogenes and tumor suppressor genes in a single test. (gotoper.com)
These recurrent genomic alterations include mutations, gene re-arrangements, and copy number changes in relevant lung cancer genes ( Figure 1 ). (gotoper.com)
16 Many of these mutations cluster around the catalytic tyrosine kinase domain of the gene of interest and result in constitutive activation of the mutant protein and down-stream pathways. (gotoper.com)
The development of targeted therapies for both germline and somatic DNA mutations has increased the need for molecular profiling assays to determine the mutational status of specific genes. (oncotarget.com)
One of the mutations that has aroused considerable interest in recent years concerns the BRAF (v-raf murine sarcoma viral oncogene homolog B) gene that encodes the protein belonging to a highly oncogenic RAS/RAF/MEK/ERK signaling pathway [ 9 ]. (hindawi.com)
These studies reveal that recurrent somatic mutations occur in only a handful of genes, with an overall mutational burden of roughly 1-2 per Mb. (springer.com)
Specific molecular therapy can target mutated cell lines in which DNA defect repair is altered, caused by mutations of BRCA2, partner and localizer of BRCA2 (PALB2), and phosphatase and tensin homolog (PTEN) or the transmembrane protease serine 2-ERG (TMPRSS2-ERG) fusion. (bjbms.org)

What pathways are this gene/protein implicaed in? (cancerindex.org)
While studies of selected MLL-fusions have revealed critical molecular pathways, unifying mechanisms across all MLL-fusions remain poorly understood. (nature.com)
In-frame fusions that produce chimeric proteins often drive cancer development and progression via dysregulation of signaling pathways related to the fusion genes. (biomedcentral.com)
The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. (oncotarget.com)
We shall consider each subtype in turn describing genes and pathways of oncogenesis and how these relate to prognosis and treatment response. (springer.com)
The upregulated DEGs were primarily protein‑coding genes enriched in immune and inflammation response pathways, while the downregulated DEGs were mainly coding long non‑coding (lnc)RNAs, indicating the regulatory function of USF1. (spandidos-publications.com)
It was also demonstrated that USF1 directly binds to the promoter region of 2,492 genes, which may be involved in the viral progression and cell proliferation pathways. (spandidos-publications.com)
The 'cancer platform' concept proposes that most oncogenic molecules also have the inherent ability to activate tumor suppressor genes or pathways through oncogene-induced apoptosis or senescence, thus limiting their oncogenic effects in a homeostatic fashion. (biomedcentral.com)
Oncogene activation is therefore generally only tumorigenic when it is coupled with inactivation or inhibition of oncogene-induced pro-apoptotic or senescence pathways [ 4 ]. (biomedcentral.com)
The specific effects that lead to inactivation of these pro-apoptotic or senescence pathways may impinge on major known tumor suppressors such as p53, but may also be due to effects on other genes and molecules within the p53 or other tumor suppressor pathways [ 5 ]. (biomedcentral.com)

For example, the TP53 gene, located on chromosome 17, encodes a 53-kd nuclear protein that functions as a cell cycle checkpoint. (medscape.com)
RB1 encodes the protein pRB and was the first tumor suppressor gene to be molecularly defined. (medscape.com)
This gene encodes a protein containing a C3HC4-type RING finger domain, which is a specialized type of Zn-finger that binds two atoms of zinc and is thought to be involved in mediating protein-protein interactions. (cancerindex.org)
The resulting mutant fusion gene sequence encodes a fusion protein that can have novel effects, or in which both portions remain functional, but are now produced in at inappropriate times and in inappropriate amounts. (skincare.nz)

Promoter region motif analysis indicated that ETV5 has more binding motifs and genes than USF1 itself for USF1‑regulated DEGs, indicating that USF1 may indirectly modulate gene expression by regulating ETV5 expression in Huh7 cells. (spandidos-publications.com)

Another important class of tumor suppressor genes involved in cell cycle control and in the generation of human cancers is the cyclin-dependent kinase (CDK) inhibitors. (medscape.com)
We benefit from our expertise in oncogenes whose involvement in each of these cancers is well documented, including tyrosine kinase activity receptors (RTK) and ETS fusion genes. (pluginlabs-hautsdefrance.fr)
The development of targeted therapies in pancreatobiliary cancers has been hampered by the difficulty in obtaining biopsies with sufficient tumor cell content for genomic sequencing analyses. (aacrjournals.org)
Fusions involving the tropomyosin-related kinase (TRK) family of neurotrophin receptor tyrosine kinases have been identified in various human cancers and suggested to function as oncogenic drivers. (aacrjournals.org)
Fusion genes feature in many cancers, a form of mutation in which two genes are joined together, such as through deletion of the DNA sequences that normally separate the two genes. (skincare.nz)
Fusion genes are also found in among others prostate, breast, lung and brain tumours: in total, in up to 20% of all cancers. (skincare.nz)
In the context of cancer gene therapy, it is clear that targeting a single gene is often insufficient to eliminate cancer cells - yet, many types of cancers are addicted to the presence of a single oncogenic event that can reprogram cells and initiate tumorigenesis . (skincare.nz)
17,20 Similar to EGFR -mutant lung cancers, for patients with ALK fusion-positive lung cancers, treatment with crizotinib is superior to chemotherapy. (gotoper.com)
21 ROS1 and RET fusions are each found in approximately 1% to 2% of unselected lung cancers, and responses to crizotinib and cabozantinib, respectively, have been described in early studies. (gotoper.com)
Here we describe the analytical validation of a custom probe-based NGS tumor panel, TumorNext, which can detect single nucleotide variants, small insertions and deletions in 142 genes that are frequently mutated in somatic and/or germline cancers. (oncotarget.com)
Correlation with outcome needs to be more comprehensively furnished, particularly for small renal masses, rarer non-clear cell renal cancers, and for all tumours undergoing targeted therapy. (springer.com)
Upstream transcription factor 1 (USF1) is a canonical transcription factor (TF) and is associated with the pathogenesis of several cancers, but its biological functions and molecular targets in HCC remain unclear. (spandidos-publications.com)
In this review, we summarize some recent findings on HPV-associated carcinogenesis, such as miRNAs in HPV-associated cancers, implication of stem cells in the biology and therapy of HPV-positive cancers, HPV vaccines, targeted therapy of cervical cancer, and drug treatment for HPV-induced intraepithelial neoplasias. (virosin.org)
Advanced and metastatic prostate cancers require systemic therapies, including hormonal inhibition, chemotherapy, and targeted agents. (bjbms.org)

This is the case for the so-called fusion oncogenes (FOs), which are chimeric genes resulting from in-frame fusions of the coding sequences of two genes involved in a chromosomal rearrangement. (skincare.nz)
Gene fusions are chimeric genes that combine at least two parental genes. (biomedcentral.com)

The TP53 gene is also capable of stimulating apoptosis of cells containing damaged DNA. (medscape.com)
TP53 activates the expression of genes involved in apoptosis, cell cycle regulation (p21), and MDM2. (medscape.com)

MLL-fusions represent a large group of leukemia drivers, whose diversity originates from the vast molecular heterogeneity of C-terminal fusion partners of MLL. (nature.com)
Numerous studies have established strong links between the molecular function of the fusion partner and the mechanistic basis of oncogenic transformation in MLL-fusion-induced leukemogenesis 4 . (nature.com)
However, it is unclear whether these molecular mechanisms pertain to the entire family of MLL-fusions or if they specifically affect the leukemogenicity of isolated MLL-fusion proteins. (nature.com)
This mechanism also applies to hematopoietic cells transformed by other HOX genes, including CDX2, which is highly expressed in a majority of acute myeloid leukemias, thus providing a molecular approach based on GSK-3 inhibitory strategies to target HOX-associated transcription in a broad spectrum of leukemias. (stanford.edu)
The overall objective of our team is to decipher the molecular mechanisms leading to oncogenic addiction, then to the process of resistance, in order to improve the effectiveness of targeted therapies. (pluginlabs-hautsdefrance.fr)
The Fibroblast Growth Factor Receptors/Fibroblast Growth Factors (FGFRs/FGFs) axis offers interesting molecular targets to be pursued in clinical development. (123dok.org)
With the advancement of personalized medicine, patients have been stratified on the basis of expression of actionable molecular targets. (123dok.org)
With this technology, researchers can target specific sequences of the genome and, as if using molecular scissors, cut and paste DNA fragments and thus modify the genome in a controlled way. (skincare.nz)
Therefore, the BRAF pathway has become a molecular target for individualized cancer therapy, with promising results deriving from clinical trials [ 10 ]. (hindawi.com)
In 2005, the first-ever trial combining small molecular targeted agent known as bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody, with doublet chemotherapy, had shown superiority of overall survival with this treatment modality in advanced non-squamous non-small cell lung cancer patients without brain metastasis [ 2 ]. (biomedcentral.com)
Current concepts suggest that a limited number of molecular alterations involving oncogene activation and tumor suppressor inhibition are responsible for initiation of cancer. (biomedcentral.com)

Gene fusions can help identify patients who are likely to respond to targeted therapies, allowing selection of the most appropriate treatment option for each patient. (biomedcentral.com)
Mechanisms of resistance to targeted therapies and evaluation of innovative therapeutic strategies. (pluginlabs-hautsdefrance.fr)
Such tumor profiles can subsequently be applied to exclusively tailor cancer therapies to directly target a causative mutation for a malignancy, ultimately achieving a personalized and precise approach to cancer treatment. (biomedcentral.com)
There are a few high-profile examples of rationally and molecularly targeted therapies, but we need to do much better if we are to shift the entire pattern of treatment to drugs that have high potency but mild side effects. (biomedcentral.com)
This review summarizes the pathophysiological mechanisms and available targeted therapies for prostate cancer. (bjbms.org)

This gene is a member of the protein-tyrosine kinase oncogene family. (cancerindex.org)

Expression of MLL-fusions enhances proliferation and blocks myeloid differentiation of hematopoietic progenitor cells, leading to their pathological accumulation. (nature.com)
Inactivation of tumor suppressor genes, whose products normally provide negative control of cell proliferation, contributes to malignant transformation in various cell types. (medscape.com)
Tumor suppressor genes encode proteins that normally provide negative control of cell proliferation. (medscape.com)
Preclinical studies demonstrated that LOXO-101 inhibited the proliferation of cancer cell lines harboring oncogenic TRK fusions in a dose-dependent manner and resulted in suppression of tumor growth in vivo , consistent with previous studies. (aacrjournals.org)

utilizes a combination of high-resolution comparative genomic hybridization, short hairpin RNA inhibition of target genes at the locations of focal genomic deletions, and a primed cell mosaic mouse model to identify novel tumor suppressors in hepatocellular carcinoma. (biomedcentral.com)

It can be used to identify high-quality gene fusions for further bioinformatic and experimental studies, including validation of genomic breakpoints and studies of the mechanisms that generate fusions. (biomedcentral.com)
CRISPR is used to induce targeted breaks in nuclear DNA at specific points relative to two well known fusion genes, with the result that the gene, if present, is skipped over and removed by the DNA repair mechanisms responsible for reassembling the broken chromosome. (skincare.nz)
Deregulation of these processes by oncogenic BRAF has been implicated in different mechanisms underlying cancer development and progression. (hindawi.com)

Germline mutation of one TP53 allele is found in patients with Li-Fraumeni syndrome who generally inherit a mutated TP53 gene from an affected parent. (medscape.com)
Currently, more than 1% of all human genes are implicated via mutation in cancer. (sanger.ac.uk)
The most promising part of this approach is that it is very specific to the cells that exhibit this fusion gene mutation. (skincare.nz)

Nussе and Varmus identified components of the Wnt/β-catenin pathway in 1982 in a study of oncogenic breast tumor viral diseases (MMTV) [1]. (chemdiv.com)
Inoculation with a high dose strains of LMP1 transgenic mice vide a powerful tool in mechanistic of EBV caused a B-cell lymphopro- were established that express LMP1 studies on the role of individual viral liferative disorder in these mice, under the control of the immunoglob- genes in cancer. (who.int)

The ability to precisely manipulate cancer cell genomes to correct or eliminate cancer-causing aberrations by highly-efficient CRISPR/Cas9 genome editing opens new possibilities to develop FO-targeted options to eliminate cancer cells. (skincare.nz)
This review summarizes the common oncogenic aberrations that occur in NSCLC and the diagnostic assays that are poised to detect them. (gotoper.com)
The next most prevalent aberrations include a cohort of chromatin-modifying genes with diverse roles including PBRM1 , SETD2 , BAP1 , and KMD5C . (springer.com)
In addition, there are only a small number of recurrent copy number aberrations and rare gene fusions. (springer.com)

MLL-fusion proteins are found in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) and are often associated with adverse prognosis, particularly in pediatric patients 3 . (nature.com)
To relate the occurrence of gene fusions to Gleason Grading Groups and disease prognosis, we performed survival analyses using the Kaplan-Meier estimator, log-rank test, and Cox regression. (biomedcentral.com)
We found evidence that the number of gene fusions was associated with the prognosis of PCa. (biomedcentral.com)
Tandem duplication involving the KIAA1549 and the BRAF kinase genes results in a gene fusion that has been recently characterized in a subset of low grade glioma While there is no clear evidence that the KIAA1549 - BRAF gene fusion has an effect on prognosis, it is an attractive target for therapy development and as a diagnostic tool. (springeropen.com)

The TRK inhibitor LOXO-101 inhibits the growth of TRK fusion-positive cells in vitro and in vivo . (aacrjournals.org)
Interestingly, we found circRNA-mediated regulation of target miRNAs and an in vivo growth inhibitory effect upon TUSC3 circ104557 transduction. (oncotarget.com)
For instance, mice are able to reconstitute most lymphomas in monkeys and humans woodchuck hepatitis virus induces major components of the human provides strong support for a direct hepatocellular carcinoma (HCC) haematolymphoid system including oncogenic role of EBV in vivo. (who.int)

Among one of the actionable targets is the fibroblast growth factor receptor (FGFR) pathway, triggered by specific ligands. (123dok.org)
Castration-resistant prostate cancer (CRPC) usually involves the PI3K/AKT/mTOR pathway and requires targeted therapy. (bjbms.org)
Proviral infection at the "site of the highest degree" was thought to be the mechanism of carcinogenesis, giving the first name to the gene found along this pathway as INT1. (chemdiv.com)

120 different translocations, resulting in the generation of MLL-fusion proteins encompassing more than 75 different partner genes 5 . (nature.com)
In cancer, genomic rearrangements can create fusion genes that either combine protein-coding sequences from two different partner genes or place one gene under the control of the promoter of another gene. (biomedcentral.com)

Search the gene expression profiles from curated DataSets in the Gene Expression Omnibus (GEO) repository. (cancerindex.org)
This can lead to the formation of a chimeric gene that combines functional domains from both fusion partner genes, or to a promoter swapping event, where the promoter of one gene is replaced with another, leading to altered gene expression. (biomedcentral.com)
2) We have discovered a group of oncoproteins that are implicated in long-term maintenance of gene expression through their effects on the state of chromatin. (stanford.edu)
The multifunctional regulator nuclear factor erythroid 2-related factor (Nrf2) is considered not only as a cytoprotective factor regulating the expression of genes coding for anti-oxidant, anti-inflammatory and detoxifying proteins, but it is also a powerful modulator of species longevity. (springer.com)
The datasets included transcriptome-wide expression and matched clinical follow-up data to detect and characterize gene fusions in PCa. (biomedcentral.com)
As a TF, USF1 has a bidirectional regulatory function, being able to regulate gene expression by activating or suppressing the promoter region of target genes ( 5 , 6 ). (spandidos-publications.com)
The roles of b-catenin are 'classically' defined: as an adhesion protein and as a signaling protein, transducing extracellular signals to the nucleus to modify gene expression. (chemdiv.com)
Systematic interrogation of gene function requires the ability to perturb gene expression in a robust and generalizable manner. (cdc.gov)
The signature of our top screening hits is significantly correlated with gene expression data from clinical melanoma samples. (cdc.gov)
Programmable DNA binding proteins have emerged as an exciting platform for engineering synthetic transcription factors for modulating endogenous gene expression 5 - 11 . (cdc.gov)
These dCas9-activator fusions targeted to the promoter region of endogenous genes can then modulate gene expression 7 - 11 . (cdc.gov)

In a clinical setting, it could help find expressed gene fusions for personalized therapy. (biomedcentral.com)
Epidermal growth factor receptor, a well-known biomarker for targeted therapy at present, was first brought up with potential clinical responsiveness to tyrosine kinase inhibitor gefitinib in 2004[ 6 ]. (biomedcentral.com)
In the current study we examine the prevalence of KIAA1549-BRAF gene fusion in pediatric patients diagnosed with low grade glioma in the Egyptian population and its relationship to clinical and histological subtypes. (springeropen.com)

It has therefore been proposed that the oncogenic activity of MLL-fusion proteins depends on chromatin targeting functions exerted by the MLL N-terminus in combination with other functional properties encoded by the fusion partners 6 . (nature.com)
We are studying the role that normal chromatin structure plays in gene regulation in hematopoietic cells and how its disruption leads to altered development and cancer. (stanford.edu)
The higher incidence of ccRCC in male patients may partially be accounted by mono-allelic inactivation of the chromatin remodelling gene, KDM5C on the X chromosome [ 6 ]. (springer.com)
Huh7 cells that overexpress USF1 were used with whole transcriptome profiling through RNA sequencing and chromatin immunoprecipitation (ChIP) sequencing methods to investigate the downstream targets of USF1. (spandidos-publications.com)

In summary, the results demonstrated that USF1 binds to the promoter region of thousands of genes and affects a large part of DEGs indirectly. (spandidos-publications.com)

Many chromosomal rearrangements and the fusion genes they produce are at the origin of childhood sarcomas and leukaemias . (skincare.nz)
However, none of the prognostic models incorporates parameters reflecting the status of chromosomal rearrangements and transcriptional disorganization in a patient sample, even though gene fusions are known to drive PCa development and progression [ 8 ]. (biomedcentral.com)

[ 1 ] His prediction was subsequently supported by the cloning of the retinoblastoma tumor suppressor gene ( RB1 ) and by functional studies of the retinoblastoma protein, Rb. (medscape.com)

As the SEC can regulate the transcriptional activity of RNA polymerase II, it was hypothesized that these MLL-fusions induce aberrant regulation of transcriptional elongation on MLL-target genes 14 . (nature.com)
Our studies have demonstrated that several of the proteins encoded by cellular oncogenes function in fundamental aspects of gene regulation. (stanford.edu)
encoded by Nfe2l2 gene) is a transcription factor responsible for the regulation of cellular redox balance and protective antioxidant and phase II detoxification responses in mammals [ 1 , 2 ]. (springer.com)
Achieving systematic, genome-scale perturbations within intact biological systems is important for elucidating gene function and epigenetic regulation. (cdc.gov)

Oncogenic KRAS drives radioresistance through upregulation of Nrf2-53BP1-mediated non-homologous end-joining repair. (cityofhope.org)

Inhibiting BRAF Oncogene-Mediated Radioresistance Effectively Radiosensitizes BRAFV600E-Mutant Thyroid Cancer Cells by Constraining DNA Double-Strand Break Repair. (cityofhope.org)
Sixty patients between the ages of 1 to 18 years were analyzed for the presence of KIAA1549-BRAF fusion gene products using reverse transcription-PCR and sequencing. (springeropen.com)
KIAA1549-BRAF fusion genes were detected in 56.6% of patients. (springeropen.com)
Several break points were identified leading to gene fusion between KIAA1549 exon 16 with BRAF exon 9 (16-9) in 60% of the cases, KIAA1549 exon 15 with BRAF exon 9 (15-9) in 25% of the cases and KIAA1549 exon 16 with BRAF exon 11 (16-11) in 10-15% of the cases [ 10 ]. (springeropen.com)
We also synthesize a library consisting of 70,290 guides targeting all human RefSeq coding isoforms to screen for genes which, upon activation, confer resistance to a BRAF inhibitor. (cdc.gov)

Unlike sequence-specific transcription factors, epigenetic regulators do not necessarily bind DNA at consensus sequences, but still achieve reproducible target binding in a manner that is cell and maturation-type specific. (frontiersin.org)

In this study, we investigated gene fusions in PCa, characterized potential novel candidates, and explored their role as prognostic markers for PCa progression. (biomedcentral.com)
Downstream genes, including lncRNA‑NEAT1 and TF‑ETV5, may also have potential functions in the regulated network by USF1 and have potential functions in the progression of HCC. (spandidos-publications.com)

Nrf2 stabilization and increase in its half-life even to 200 min [ 9 ] allows nuclear translocation and activation of transcription of cytoprotective genes (Fig. 1 ). (springer.com)
We use these engineered Cas9 activation complexes to investigate sgRNA targeting rules for effective transcriptional activation, demonstrate multiplexed activation of 10 genes simultaneously, and upregulate long intergenic non-coding RNA (lincRNA) transcripts. (cdc.gov)

Background: Spitzoid morphology in familial melanoma has been associated with germline variants in POT1, a telomere maintenance gene (TMG), suggesting a link between telomere biology and spitzoid differentiation. (bvsalud.org)

In cancer, gene fusions occur frequently due to the genetic instability of cancer cells. (biomedcentral.com)

A 41-year-old woman who presented with undifferentiated soft-tissue sarcoma and lung metastases was found to harbor a gene fusion consisting of the 5′ region of lamin A/C ( LMNA ) and the 3′ region of neurotrophic tyrosine kinase receptor type 1 ( NTRK1 , encoding TRKA). (aacrjournals.org)

Like Rb protein, many of the proteins encoded by tumor suppressor genes act at specific points in the cell cycle. (medscape.com)

A growing body of evidence indicates that epigenetic regulators rely, amongst other factors, on their interaction with untranslated RNA molecules for guidance to particular targets on DNA. (frontiersin.org)
Some have been shown to bind epigenetic regulators, and thus constitute attractive candidates to mediate epigenetic target specificity. (frontiersin.org)

These fusion genes can act as oncogenic drivers in tumor development and several fusions involving kinases have been successfully exploited as drug targets. (biomedcentral.com)

G protein-coupled receptors are transmembrane proteins that help to regulate a wide array of biological processes, which makes them important drug targets. (elifesciences.org)
By convention, clinicians typically focus on specific sets of key genetic markers associated with diseases, to identify the most probable drug targets. (biomedcentral.com)

Families of related leukemia fusion proteins that share genomic and biological properties represent unique opportunities to study how the combination of distinct functional protein modules can drive oncogenic transformation. (nature.com)
Genes involved in oncogenic fusions are included in Tier 1 when changes to their function caused by the fusion drives oncogenic transformation, or in cases when they provide regulatory elements to their partners (e.g. active promoter or dimerisation domain). (sanger.ac.uk)

An oncogenic LMNA-NTRK1 fusion gene was detected in a patient with metastatic soft-tissue sarcoma. (aacrjournals.org)
In a new study, researchers worked with cell lines and mouse models of Ewing's sarcoma and chronic myeloid leukaemia , in which they managed to eliminate the tumour cells by cutting out the fusion genes causing the tumour. (skincare.nz)

We discuss the value of lncRNAs as putative diagnostic, prognostic and therapeutic targets in myeloid leukemias and indicate novel directions in this exciting research field. (frontiersin.org)
Because they are only present in tumour cells, fusion genes attract a great deal of interest among the scientific community because they are highly specific therapeutic targets, and attacking them only affects the tumour and has no effect on healthy cells. (skincare.nz)

Men of European descent with higher genetic risk were diagnosed earlier, had less genomic instability, and fewer driver genes mutated. (stanford.edu)
Senescent hepatocytes lose the telomeric repeats that protect chromosomal ends from inter- and intra-chromosomal fusion, deletion, rearrangement, and transposition events that contribute to genomic instability. (biomedcentral.com)

The neoplastic cells in these neoplasms contain chromosomal translocations which create one of two fusion genes: the FUS-DDIT3 in ~90% and the EWSR1-DDIT3 fusion gene in up to 10% of myxoid liposarcoma cases. (wikipedia.org)
The largest family of "multi-partner translocations" in acute leukemia comprises fusions involving the product of the KMT2A ( MLL) gene. (nature.com)
In particular we are grateful to Felix Mitelman and his colleagues in providing information on more genes involved in uncommon translocations in leukaemias and lymphomas. (sanger.ac.uk)

Following detection, we annotated the gene fusions using published databases for gene fusions in cancer. (biomedcentral.com)

There is a total of seven signalling receptors, encoded by four FGFR genes, FGFR1-4 [15]. (123dok.org)

Non (protein)-coding RNAs are the most abundant transcriptional products of the coding genome, and comprise several different classes of molecules with unique lengths, conformations and targets. (frontiersin.org)
Such technological improvements enable a large number of molecules, including genes, transcripts, and proteins to be simultaneously measured in different conditions over time. (biomedcentral.com)

Recurrent gene rearrangements involving ALK, ROS1, RET, and NTRK have emerged as important drivers of tumor growth in lung cancer. (gotoper.com)

The FUS-DDIT3 fusion gene forms by a merger of part of the FUS FET gene family gene normally located at band 11.2 on the short (or "p") arm of chromosome 16 with part of the DDIT3 ETS transcription factor family gene normally located at band 13.3 on the long (or "q") arm of chromosome 12. (wikipedia.org)
The EWSR1-DDIT3 fusion gene forms by a merger of the EWSR1 FET gene family gene located at band 12.2 on the q arm of chromosome 22 with part of the DDIT3 gene. (wikipedia.org)
This gene is also a translocation partner in anaplastic large cell lymphoma and inflammatory myofibroblastic tumor cases, where a t(2;17)(p23;q25) translocation has been identified with the anaplastic lymphoma kinase (ALK) gene on chromosome 2, and a t(8;17)(q24;q25) translocation has been identified with the MYC gene on chromosome 8. (cancerindex.org)

These are frequently activated by fusion to other transcriptional proteins resulting in chimeric transcription factors. (stanford.edu)

Direct evidence linking the INK4A locus to tumorigenesis was provided by the targeted disruption of exon 2 of INK4A in mice. (medscape.com)

By integrating these two datasets, 16 overlapped genes were detected, including downregulated lncRNA‑NEAT1 and upregulated TF‑ETV5. (spandidos-publications.com)

Our strategy was to make two cuts in introns , non-coding regions of a gene, located at both ends of the fusion gene. (skincare.nz)

Using cancer as an example, we review how network biology can facilitate system-wide approaches to identify targeted small molecule inhibitors. (biomedcentral.com)

Anatomy2

Organisms1

Diseases2

Chemicals and Drugs14

Analytical, Diagnostic and Therapeutic Techniques and Equipment10

Phenomena and Processes23

Information Science3

Proto-oncogenes4

Tumors12

Mutations17

Pathways10

Encodes4

Indicating that USF1 may indirectly1

Cancers14

Chimeric genes2

Apoptosis2

Molecular11

Therapies5

Protein-tyrosi1

Proliferation4

Inhibition1

Mechanisms3

Mutation3

Viral2

Aberrations4

Prognosis4

Vivo3

Pathway3

Different partner genes2

Expression11

Clinical3

Chromatin4

Promoter region1

Chromosomal rearrangements2

Tumor supp1

Regulation4

Upregulation1

BRAF5

Sequences1

Progression2

Activation2

Germline1

Genetic instability1

Tyrosine Kinase1

Proteins encoded1

Epigenetic2

Kinases1

Drug targets2

Transformation2

Sarcoma2

Therapeutic targets2

Instability2

Translocations3

Detection1

Receptors1

Molecules2

Rearrangements1

Chromosome3

Transcription factors1

Tumorigenesis1

DataSets1

Introns1

Small-molecule1