Abstract
The epidermal growth factor receptor (EGFR) is a membrane-bound, 170 kDa, protein tyrosine kinase that plays an important role in tumorigenesis. The EGFR gene, which is composed of over 168 kb of sequence, including a 123-kb first intron, is frequently amplified and rearranged in malignant gliomas leading to the expression of oncogenic deletion (DM) and tandem duplication (TDM) mutants. The most common DM in gliomas is EGFRvIII, which arises from recombination between introns 1 and 7 with deletion of exons 2 through 7 and intervening introns. In addition, some human gliomas express 180- to 190-kDa TDM, which are constitutively active and highly oncogenic. Both DM and TDM arise by recombination of introns that contain sequences with homology to the recombination signal sequence (RSS) heptamers and nonamers present in the V(D)J region of the immunoglobin and T lymphocyte antigen receptor genes. V(D)J RSS have also been identified in certain proto-oncogenes like bcl-2 that are involved in translocations associated with the development of human lymphomas and in other genes such as hypoxanthine-guainine phosphoribosyl transferase (HPRT) in which deletion mutations and intron rearrangements are a common phenomenon. Together with the expression of recombination associated gene (RAG) and nonhomologous end-joining (NHEJ) proteins in gliomas, these observation suggest that aberrant activity of the V(D)J recombinase may be involved in the activation of proto-oncogenes in both liquid and solid tumors.
Keywords: egfr, egfrv, glioma, intron recombination, tandem duplication, v(d)j
Current Genomics
Title: EGFR Intron Recombination in Human Gliomas: Inappropriate Diversion of V(D)J Recombination?
Volume: 8 Issue: 3
Author(s): Robert A. Fenstermaker and Michael J. Ciesielski
Affiliation:
Keywords: egfr, egfrv, glioma, intron recombination, tandem duplication, v(d)j
Abstract: The epidermal growth factor receptor (EGFR) is a membrane-bound, 170 kDa, protein tyrosine kinase that plays an important role in tumorigenesis. The EGFR gene, which is composed of over 168 kb of sequence, including a 123-kb first intron, is frequently amplified and rearranged in malignant gliomas leading to the expression of oncogenic deletion (DM) and tandem duplication (TDM) mutants. The most common DM in gliomas is EGFRvIII, which arises from recombination between introns 1 and 7 with deletion of exons 2 through 7 and intervening introns. In addition, some human gliomas express 180- to 190-kDa TDM, which are constitutively active and highly oncogenic. Both DM and TDM arise by recombination of introns that contain sequences with homology to the recombination signal sequence (RSS) heptamers and nonamers present in the V(D)J region of the immunoglobin and T lymphocyte antigen receptor genes. V(D)J RSS have also been identified in certain proto-oncogenes like bcl-2 that are involved in translocations associated with the development of human lymphomas and in other genes such as hypoxanthine-guainine phosphoribosyl transferase (HPRT) in which deletion mutations and intron rearrangements are a common phenomenon. Together with the expression of recombination associated gene (RAG) and nonhomologous end-joining (NHEJ) proteins in gliomas, these observation suggest that aberrant activity of the V(D)J recombinase may be involved in the activation of proto-oncogenes in both liquid and solid tumors.
Export Options
About this article
Cite this article as:
Fenstermaker A. Robert and Ciesielski J. Michael, EGFR Intron Recombination in Human Gliomas: Inappropriate Diversion of V(D)J Recombination?, Current Genomics 2007; 8 (3) . https://dx.doi.org/10.2174/138920207780833838
DOI https://dx.doi.org/10.2174/138920207780833838 |
Print ISSN 1389-2029 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5488 |
Call for Papers in Thematic Issues
Advanced AI Techniques in Big Genomic Data Analysis
The thematic issue on "Advanced AI Techniques in Big Genomic Data Analysis" aims to explore the cutting-edge methodologies and applications of artificial intelligence (AI) in the realm of genomic research, where vast amounts of data pose both challenges and opportunities. This issue will cover a broad spectrum of AI-driven strategies, ...read more
Advanced Computational Algorithms and Artificial Intelligence in Clinical Pharmacogenomics
In the era of personalized medicine, understanding the relationship between genetics and drug response is crucial. This issue delves into innovative methodologies, leveraging deep computational analysis and artificial intelligence, to enhance the field of Clinical Pharmacogenomics. The interdisciplinary approach harnesses the power of advanced high-throughput genotyping technologies, sophisticated computational analysis, ...read more
Applications of Single-cell Sequencing Technology in Reproductive Medicine
Single cell sequencing (SCS) technology utilizes individual cells' genetic material to sequence their genome, transcriptome, and epigenetics at the molecular level. It offers insights into cell heterogeneity and enables the study of limited biological materials. Since its recognition as a valuable technique in 2011, single cell sequencing has yielded numerous ...read more
Big Data in Cancer Research
Cancer is a significant threat to human life and health, remaining a highly aggressive killer. It is a leading cause of death worldwide and represents a crucial medical issue for humanity. However, in the past decade, the effectiveness of new synthetic anticancer agents has not matched the current clinical speculation. ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
C-Methionine PET/CT in Central Nervous System Tumours: A Review
Current Radiopharmaceuticals MicroRNA-21 as a Novel Therapeutic Target
Current Cancer Therapy Reviews Multi-Targeted Agents in Cancer Cell Chemosensitization: What We Learnt from Curcumin Thus Far
Recent Patents on Anti-Cancer Drug Discovery Mutations in MicroRNA Genes and Their Binding Sites are Infrequently Associated with Human Colorectal Cancer in the Kashmiri Population
MicroRNA Meet Our Editorial Board Member
Current Neuropharmacology Systemic Redox Biomarkers in Neurodegenerative Diseases
Current Drug Metabolism Toxicological Profile of Therapeutic Nanodelivery Systems
Current Drug Metabolism Editorial [Hot Topic:Angiogenesis Agents(Executive Editor: Cezary Marcinkiewicz)]
Current Pharmaceutical Design On the Nature of the Tumor-Initiating Cell
Current Stem Cell Research & Therapy Autophagy as a Molecular Target of Flavonoids Underlying their Protective Effects in Human Disease
Current Medicinal Chemistry Can Dietary Antioxidants Reduce the Incidence of Brain Tumors?
Current Drug Metabolism Immune Checkpoint Regulators: A New Era Toward Promising Cancer Therapy
Current Cancer Drug Targets Role of Hsp70 in Cancer Growth and Survival
Protein & Peptide Letters Novel Therapeutic Approaches Targeting Vascular Endothelial Growth Factor and its Receptors in Haematological Malignancies
Current Cancer Drug Targets Anticarcinogenic Actions of Tributyrin, A Butyric Acid Prodrug
Current Drug Targets Role of Serum and Glucocorticoid-Inducible Kinase (SGK)-1 in Senescence: A Novel Molecular Target Against Age-Related Diseases
Current Medicinal Chemistry P53 Family: At the Crossroads in Cancer Therapy
Current Medicinal Chemistry Resistance of Cancer Cells to Targeted Therapies Through the Activation of Compensating Signaling Loops
Current Signal Transduction Therapy Rac-1 as a New Therapeutic Target in Cerebro- and Cardio-Vascular Diseases
Current Drug Targets Cruciferous Plants: Phytochemical Toxicity Versus Cancer Chemoprotection
Mini-Reviews in Medicinal Chemistry