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  • anaplastic lympho
  • Echinoderm microtubule-associated protein-like 4 and the anaplastic lymphoma kinase (EML4-ALK) fusion genes were identified in a subset of NSCLCs in 2007 (Soda et al. (springeropen.com)
  • Anaplastic lymphoma kinase (ALK) also known as ALK tyrosine kinase receptor or CD246 (cluster of differentiation 246) is an enzyme that in humans is encoded by the ALK gene. (wikipedia.org)
  • The translocation creates a fusion gene consisting of the ALK (anaplastic lymphoma kinase) gene and the nucleophosmin (NPM) gene: the 3' half of ALK, derived from chromosome 2 and coding for the catalytic domain, is fused to the 5' portion of NPM from chromosome 5. (wikipedia.org)
  • Ceritinib was approved by the FDA in April 2014 for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. (wikipedia.org)
  • Some of the most important kinases that have been shown to undergo rearrangement in human cancers include the anaplastic lymphoma kinase (ALK), ROS1 kinase, and the neurotrophic receptor tyrosine kinases (NTRKs). (wikipedia.org)
  • targets
  • Interestingly, we demonstrate that the expression of TDRD1, the topmost overexpressed gene of our list of ERG-specific candidate targets, is inversely correlated with the methylation levels of a CpG island found at -66 bp of the transcription start site in PCa and that TDRD1 expression is regulated by direct binding of ERG to the CpG island in VCaP cells. (ox.ac.uk)
  • We conclude that ETS transcription factors regulate specific and shared target genes and that TDRD1, FKBP10, and GRPR are promising therapeutic targets and can serve as diagnostic markers for molecular subtypes of PCa harboring specific fusion gene rearrangements. (ox.ac.uk)
  • On the basis of the documented effects on both local and systemic disease, it is widely perceived that combined modality therapy with suppression of the AR axis simultaneously enhances the cytotoxic effects of radiotherapy on the primary prostate cancer and also targets occult metastases. (aacrjournals.org)
  • What's exciting is that these gene fusions and rearrangements can give us targets for potential therapies," says Arul Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology, Howard Hughes Medical Institute Investigator, and S.P. Hicks Professor of Pathology at the U-M Medical School. (healthcanal.com)
  • Deletion lengthening at chromosomes 6q and 16q targets multiple tumor suppressor genes and is associated with an increasingly poor prognosis in prostate cancer. (nih.gov)
  • Gene rearrangements, leading to the expression of constitutively activated fusion tyrosine kinase receptors, have been increasingly identified as a common feature of malignancies over the last three decades, and success has been demonstrated using these rearrangements as targets for drug development. (wikipedia.org)
  • kinase
  • The recurrent patterns were seen in the MAST kinase and Notch family genes. (healthcanal.com)
  • Entrectinib (RXDX-101) is a selective tyrosine kinase inhibitor developed by Ignyta, Inc., with specificity, at low nanomolar concentrations, for all of three Trk proteins (encoded by the three NTRK genes, respectively) as well as the ROS1, and ALK receptor tyrosine kinases. (wikipedia.org)
  • The expression of such gene fusions in a tumor can create a phenomenon termed 'oncogene addiction' in which the tumor becomes dependent on signaling by the aberrant kinase pathway, thus rendering its survival and continued proliferation exquisitely sensitive to targeted inhibition with small molecule tyrosine kinase inhibitor drugs. (wikipedia.org)
  • Expression of the proteins encoded by these tyrosine kinase fusion genes can, in most cases, be shown to function independently as oncogenic drivers, capable of activating critical downstream pathways involved in the malignant phenotype, resulting in transformation of cells in vitro. (wikipedia.org)
  • Cell division protein kinase 6 (CDK6) is an enzyme encoded by the CDK6 gene. (wikipedia.org)
  • The protein encoded by this gene is a member of the cyclin-dependent kinase, (CDK) family, which includes CDK4. (wikipedia.org)
  • This kinase, as well as CDK4, has been shown to phosphorylate, and thus regulate the activity of, tumor suppressor Retinoblastoma protein making CDK6 an important protein in cancer development. (wikipedia.org)
  • tumors
  • These types of genetic recombinations have previously been linked to blood cancers and rare soft-tissue tumors, but are beginning to be discovered in common solid tumors, including a large subset of prostate cancers and some lung cancers. (healthcanal.com)
  • Looking at the genetic sequencing of 89 breast cancer cell lines and tumors, researchers found two distinct types of genetic rearrangements that appear to be driving this subset of breast cancers. (healthcanal.com)
  • The research provides additional evidence that these types of genetic rearrangements seem to be a significant cause of solid tumors," he adds. (healthcanal.com)
  • Gene sequencing offers opportunities to develop treatments for individuals whose tumors carry specific genetic combinations - a process commonly known as "personalized medicine. (healthcanal.com)
  • Its prevalence across cancers is not known, because only a few types of tumors have been analyzed for chromoplexy in the published literature. (wikipedia.org)
  • However, it was detected in the majority of 57 prostate tumors analyze and has been reported in non-small cell lung cancers, melanoma and head and neck squamous cell cancers Along with chromothripsis, and break-fusion-bridge cycles, chromoplexy is an example of chromoanagenesis. (wikipedia.org)
  • Tumors are collected from metastatic sites and the prostate, when present, and thus constitute a valuable resource to study the natural history and evolution of prostate cancer ( 2 , 3 ). (aacrjournals.org)
  • EML4-ALK-rearrangement in NSCLC is exclusive and not found in EGFR- or KRAS-mutated tumors. (wikipedia.org)
  • Interim results from two ongoing phase 1 trials have been reported at the 2016 AACR American Association for Cancer Research Conference in April 2016: among the patients treated with entrectinib, four patients had tumors harboring NTRK fusions, including patients with non-small cell lung cancer (NSCLC), mCRC, salivary gland cancer, and astrocytoma. (wikipedia.org)
  • The preliminary results seen with entrectinib in the phase I studies of patients with NTRK/ROS1/ALK fusions have led to the initiation of an open-label, multicenter, global, phase II basket study to examine the use of entrectinib in patients having tumors with these gene rearrangements. (wikipedia.org)
  • 2016
  • For a "Cancer Dialogue" held during the 2016 American Association of Cancer Research (AACR) Annual Meeting, half a dozen stellar participants from the resea. (ascopost.com)
  • Excitement was high on the last day of the 2016 Annual Meeting of the American Association for Cancer Research (AACR) in anticipation of Vice President Joseph R. Biden's remarks related to the Moonsho. (ascopost.com)
  • Proteins
  • The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. (wikipedia.org)
  • The proteins made by both genes are essential for repairing damaged DNA (see Figure of recombinational repair steps). (wikipedia.org)
  • TMPRSS2
  • In prostate cancers containing ETS+gene fusions (such as TMPRSS2-ERG), chromoplexy breakpoints are generally clustered within actively transcribed DNA and open chromatin. (wikipedia.org)
  • Recurrent gene fusions between the androgen-regulated gene TMPRSS2 and the ETS transcription factor family members ERG, ETV1 , and ETV4 have been identified as a critical event in prostate cancer development. (aacrjournals.org)
  • We used a fluorescence in situ hybridization (FISH) split probe strategy to comprehensively evaluate TMPRSS2 -ETS aberrations across 97 nonosseous metastatic sites of prostate cancer from 30 rapid autopsies of men who died of androgen-independent disease. (aacrjournals.org)
  • Tissue microarrays were constructed representing multiple metastatic sites from each patient, and split signal FISH probes for TMPRSS2, ERG, ETV1 , and ETV4 were used to assess for TMPRSS2- ETS rearrangements. (aacrjournals.org)
  • The most common prostate cancer gene fusion, TMPRSS2-ERG , can be generated by the mechanism of interstitial deletion (Edel) about 39% to 60% of the time in clinically localized disease. (aacrjournals.org)
  • Interestingly, we observed that all of the androgen-independent metastatic prostate cancer sites harboring TMPRSS2-ERG were associated with Edel. (aacrjournals.org)
  • These findings suggest that TMPRSS2-ERG with Edel is an aggressive and, in this study, uniformly lethal molecular subtype of prostate cancer associated with androgen-independent disease. (aacrjournals.org)
  • We recently identified the fusion of the 5′-untranslated region of TMPRSS2 (21q22.3) with the ETS family members ERG (21q22.2), ETV1 (7q21.2), or ETV4 (17q21) in prostate cancer ( 4 , 5 ) that has subsequently been confirmed by multiple groups ( 6 - 9 ). (aacrjournals.org)
  • We also showed that most prostate cancers harboring gene rearrangements can be identified using a 5′ and 3′ split probe fluorescence in situ hybridization (FISH) strategy with probes tightly flanking the TMPRSS2, ERG, ETV1 , and ETV4 loci ( 4 , 5 , 11 ). (aacrjournals.org)
  • Using this approach, 65% of clinically localized prostate cancers showed TMPRSS2 rearrangement, with the majority (55%) being fused to ERG ( 11 ). (aacrjournals.org)
  • Hence, we sought to characterize the frequency, mechanism, and significance of TMPRSS2 -ETS aberrations in a rapid autopsy cohort of 30 American men who died of androgen-independent metastatic prostate cancer. (aacrjournals.org)
  • BRCA2
  • Large rearrangements are less frequent in the BRCA2 gene than in BRCA1 . (beds.ac.uk)
  • We report, here, the first total deletion of exon 3 in the BRCA2 gene that was detected during screening of 2058 index cases from breast/ovarian cancer families for BRCA2 large rearrangements. (beds.ac.uk)
  • Large BRCA2 rearrangements were analysed by QMPSF (Quantitative Multiplex PCR of Short Fluorescent Fragments) or MLPA (Multiplex Ligation-Dependent Probe Amplification). (beds.ac.uk)
  • The exon 3 deletion was characterized with a "zoom-in" dedicated CGH array to the BRCA2 gene and sequencing. (beds.ac.uk)
  • This study reports the first large rearrangement of the BRCA2 gene that includes all of exon 3 and leads to an in frame deletion of exon 3 at the transcriptional level. (beds.ac.uk)
  • This paper highlights that large rearrangements and total deletion of exon 3 in the BRCA2 gene could contribute to hereditary breast and/or ovarian cancer. (beds.ac.uk)
  • The BRCA2 gene (MIM#600185) is a tumour suppressor gene that codes for a 3,418 amino-acid protein. (beds.ac.uk)
  • In contrast to the BRCA1 gene, reports of large rearrangements in the BRCA2 gene are rare. (beds.ac.uk)
  • Additionally, for the first time, a novel large rearrangement in the BRCA2 gene (Δ3 LR) that leads to a complete in frame deletion of exon 3 has been identified. (beds.ac.uk)
  • BRCA2 and BRCA2 (/ˌbrækəˈtuː/) are a human gene and its protein product, respectively. (wikipedia.org)
  • The official symbol (BRCA2, italic for the gene, nonitalic for the protein) and the official name (breast cancer 2) are maintained by the HGNC. (wikipedia.org)
  • If BRCA1 or BRCA2 itself is damaged by a BRCA mutation, damaged DNA is not repaired properly, and this increases the risk for breast cancer. (wikipedia.org)
  • Although the structures of the BRCA1 and BRCA2 genes are very different, at least some functions are interrelated. (wikipedia.org)
  • Like BRCA1, BRCA2 probably regulates the activity of other genes and plays a critical role in embryo development. (wikipedia.org)
  • Certain variations of the BRCA2 gene increase risks for breast cancer as part of a hereditary breast-ovarian cancer syndrome. (wikipedia.org)
  • People who have two mutated copies of the BRCA2 gene have one type of Fanconi anemia. (wikipedia.org)
  • subtypes
  • We found specific deregulation of 57 genes in ERG-positive PCa and 15 genes in ETV1-positive PCa, whereas deregulation of 27 genes was shared in both tumor subtypes. (ox.ac.uk)
  • In a meta-analysis of neoadjuvant studies totaling over 18,000 patients, achievement of pathologic complete response was associated with significantly reduced disease recurrence and mortality across the various breast cancer subtypes. (ascopost.com)
  • novel
  • Bipolar castration and stimulation that contributes to increasing DNA damage represents a novel strategy of sensitizing prostate cancer to cytotoxic therapies, including radiotherapy. (aacrjournals.org)
  • In this issue of Clinical Cancer Research , Hedayati and colleagues ( 1 ) report a novel, but possibly counterintuitive, strategy of exploiting sequential androgen suppression and stimulation to increasingly sensitize prostate cancer cells to radiotherapy. (aacrjournals.org)
  • W illiam G. Kaelin, Jr, MD , Chair of the Executive Committee for Research at Dana-Farber Cancer Institute, received the 10th annual Princess Takamatsu Award for "novel and significant work" in cancer from the American Association for Cancer Research (AACR). (ascopost.com)
  • This rearrangement occurs early in the differentiation process and creates novel T-cell receptors that mimic the structure of normal antibodies but are not able to function properly. (wikipedia.org)
  • clinical
  • As part of our mission to eliminate cancer, MD Anderson researchers conduct hundreds of clinical trials to test new treatments for both common and rare cancers. (mdanderson.org)
  • These data can also be used to help determine clinical trial eligibility for patients with alterations in genes not amenable to current FDA-approved targeted therapies. (mayomedicallaboratories.com)
  • Alterations in the expression of cytoskeletal regulatory genes and migration properties of BCP represent early events in the evolution of the disease, from the preleukemic phase to the clinical onset, and suggest new strategies for effective eradication of leukemia. (aacrjournals.org)
  • We assessed the association between ERG rearrangement status and clinical benefit from abiraterone acetate. (aacrjournals.org)
  • Hugh J. Jewett developed the first clinical staging of bladder cancer, created the basis for our modern-day staging of bladder cancer and developed a prognostic model that could be easily shared among physicians and patients. (jhu.edu)
  • An open label, multicenter, global phase 2 clinical trial called STARTRK-2 is currently underway to test the drug in patients with ROS1/NTRK/ALK gene rearrangements. (wikipedia.org)
  • protein
  • Inhibitor of growth protein 1 is a protein that in humans is encoded by the ING1 gene. (wikipedia.org)
  • The protein encoded by this gene belongs to a group of apparently inactive homologs of ubiquitin-conjugating enzymes. (wikipedia.org)
  • S100 calcium-binding protein A2 (S100A2) is a protein that in humans is encoded by the S100A2 gene. (wikipedia.org)
  • Zinc finger protein Rlf is a protein that in humans is encoded by the RLF gene. (wikipedia.org)
  • The first 140 amino acids of the TMEM106A protein, including portions of DUF1356 and a transmembrane region, are deleted along with BRCA1 during early-onset breast cancer. (wikipedia.org)
  • T-cell leukemia homeobox protein 3 is a protein that in humans is encoded by the TLX3 gene. (wikipedia.org)
  • The human reference BRCA 2 gene contains 27 exons, and the cDNA has 10,254 base pairs coding for a protein of 3418 amino acids. (wikipedia.org)
  • genetic
  • The study demonstrated that the genetic rearrangements had profound effects on breast cancer cells in the lab, both in tissue culture and in mouse models. (healthcanal.com)
  • Screening for breast and prostate cancer based on genetic risk factors as well as age could reduce the number of people screened without a significant reduction in the number of cancers detected, a new study suggests. (bionews.org.uk)
  • For our model to be used women would need to have a genetic test before the age of 35', said Dr Pashayan, explaining how the approach would work in breast cancer screening. (bionews.org.uk)
  • Using nurses to pre-screen people for genetic risk of cancer, cardiac or endocrine disease before they're sent to specialist services can reduce referrals by up to 75 percent, a preliminary trial has found. (bionews.org.uk)
  • Edel
  • However, our data suggest that 2+ Edel cancers, accounting for 15% of all mCRPC patients and previously associated with a worse outcome, derived the greatest benefit. (aacrjournals.org)
  • NSCLC
  • 2009 ). In recent years, because of the development of biomarker-driven personalized therapy, the treatment approach for many cancers including the NSCLC has changed (Vagulienė et al. (springeropen.com)
  • The ALK rearrangements that are found in up to 5 % of patients with NSCLC are related to younger age, no history of smoking and distinct clinicopathological features such as adenocarcinoma histology (Shaw et al. (springeropen.com)
  • NSCLC accounts for about 85% of all lung cancers. (wikipedia.org)
  • smokers
  • Pie chart showing incidences of non-small cell lung cancers as compared to small cell carcinoma shown at right, with fractions of smokers versus non-smokers shown for each type. (wikipedia.org)
  • ALK lung cancers are more common in light cigarette smokers or nonsmokers, but a significant number of patients with this disease are current or former cigarette smokers. (wikipedia.org)
  • expression
  • The expression of genes regulating the cytoskeleton was also affected, resulting in a block of CDC42 signaling. (aacrjournals.org)
  • We performed differential expression analysis on nine normal prostate tissues and 50 PCa enriched for different ETS rearrangements using exon-level expression microarrays, followed by in vitro validation using cell line models. (ox.ac.uk)
  • Heterogeneity of ERG expression in prostate cancer: a large section mapping study of entire prostatectomy specimens from 125 patients. (nih.gov)
  • Shamir used his expertise in graph theory to develop clustering algorithms for analyzing gene expression problems. (wikipedia.org)
  • He developed extensive lecture notes which are in broad use on Computational Genomics (Algorithms for Molecular Biology) and on Analysis of Gene Expression, DNA Chips and Gene Networks. (wikipedia.org)
  • It shows tissue-enriched gene (TEG) expression when compared to housekeeping gene (HKG) expression. (wikipedia.org)
  • There are many changes in gene expression that are regulated through this enzyme. (wikipedia.org)
  • detect
  • A semi-automated PCR method involving fluorescent-labeled PCR products and non-denaturing capillary electrophoresis is performed to detect only complete TCRB rearrangements. (mdanderson.org)