Oncogene

Oncogene
Name	Oncogene
Field	Molecular oncology
Discovered	1960s–1970s

Oncogene Oncogenes are genes that, when altered by mutation, amplification, or aberrant regulation, can drive cellular transformation and malignant phenotypes. They were first recognized through comparative studies of viral transforming genes and cellular counterparts, and they remain central to translational research linking basic molecular biology to clinical oncology. Research on oncogenes integrates work across institutions and consortia to inform diagnostics, prognostics, and targeted therapies.

Definition and Historical Discovery

The concept emerged from studies of Rous sarcoma virus, Howard Temin, David Baltimore, Francis Peyton Rous, and the discovery of viral oncogenes such as src, which led to identification of cellular proto-oncogenes by teams at National Institutes of Health, Cold Spring Harbor Laboratory, Salk Institute, and universities including Harvard University and Stanford University. Key figures include J. Michael Bishop and Harold Varmus whose work on cellular homologs of viral oncogenes earned a Nobel Prize and connected viral transformation to normal cellular genes. Early molecular cloning by laboratories at Cambridge University, University of California, Berkeley, and Massachusetts Institute of Technology enabled characterization of families such as ras, myc, and erbB, with follow-up studies at research centers including Wellcome Trust-supported units and the European Molecular Biology Laboratory.

Classification and Molecular Mechanisms

Oncogenes are classified by biochemical function and alteration type: mutated signaling molecules (e.g., members of the RAS family), transcription factors (e.g., MYC), receptor tyrosine kinases (e.g., EGFR, HER2/neu), intracellular kinases (e.g., BRAF, ABL1), and fusion oncoproteins resulting from chromosomal translocations (e.g., BCR-ABL1, PML-RARA). Mechanisms include point mutation, gene amplification, chromosomal rearrangement, and insertional mutagenesis demonstrated in studies at Cold Spring Harbor Laboratory, Johns Hopkins University, MD Anderson Cancer Center, and Fred Hutchinson Cancer Research Center. Signaling pathways affected include the MAPK/ERK pathway, PI3K-AKT pathway, and JAK-STAT pathway—concepts elaborated in textbooks from Oxford University Press and reviews in journals such as Nature, Science, and Cell. Structural biology contributions from groups at European Synchrotron Radiation Facility, Brookhaven National Laboratory, and Max Planck Institute clarified kinase domains and oncogenic activation, informing inhibitor design.

Role in Cancer Development and Progression

Oncogenes cooperate with loss of tumor suppressors such as TP53, RB1, and PTEN to enable hallmarks of cancer described by authors at Harvard Medical School and institutions contributing to the National Cancer Institute programs. Specific oncogenes have been linked to tumor types: KRAS in pancreatic and colorectal carcinomas studied at Memorial Sloan Kettering Cancer Center; BRAF V600E in melanoma characterized by collaborative work at Dana-Farber Cancer Institute; and EGFR mutations identified in lung adenocarcinoma samples collected by consortia including The Cancer Genome Atlas and International Cancer Genome Consortium. Oncogene-driven processes include uncontrolled proliferation, evasion of apoptosis, metabolic reprogramming described by researchers at Weizmann Institute of Science, and metastasis studied in labs at University of Cambridge and Karolinska Institutet.

Detection, Diagnostic and Prognostic Applications

Detection of oncogene alterations uses methods developed at centers like Broad Institute and commercial laboratories including Foundation Medicine: Sanger sequencing pioneered at Cold Spring Harbor Laboratory, next-generation sequencing platforms from Illumina and Thermo Fisher Scientific, fluorescence in situ hybridization techniques refined at Memorial Sloan Kettering Cancer Center, and quantitative PCR assays used in clinical labs at Mayo Clinic. Biomarker panels incorporating alterations in ALK, ROS1, MET, and ERBB2 inform therapy selection in guidelines from organizations such as American Society of Clinical Oncology and European Society for Medical Oncology. Prognostic significance of oncogene status has been established in cohort studies coordinated by SEER Program and multicenter trials run by cooperative groups like Eastern Cooperative Oncology Group and Cancer Research UK.

Therapeutic Targeting and Drug Development

Targeted therapies emerged from translational pipelines at pharmaceutical firms like Roche, Pfizer, Novartis, Bristol-Myers Squibb, and biotech companies such as Genentech and Amgen. Milestones include development of kinase inhibitors (e.g., imatinib targeting BCR-ABL1), monoclonal antibodies (e.g., trastuzumab targeting HER2), and small-molecule inhibitors against EGFR, ALK, and BRAF validated in randomized trials at National Cancer Institute-sponsored cooperative groups. Resistance mechanisms driven by secondary mutations, bypass signaling, and tumor heterogeneity described by teams at University of Texas MD Anderson Cancer Center and Fred Hutchinson Cancer Research Center have led to combination regimens and next-generation inhibitors developed in collaborations with regulators such as U.S. Food and Drug Administration and European Medicines Agency.

Experimental Models and Research Methods

Experimental systems include genetically engineered mouse models from labs at The Jackson Laboratory and Cold Spring Harbor Laboratory, patient-derived xenografts established by investigators at Huntsman Cancer Institute and Memorial Sloan Kettering Cancer Center, and CRISPR/Cas9 screens developed at Broad Institute and MIT. High-throughput drug screens use platforms created at Scripps Research Institute and GlaxoSmithKline; single-cell sequencing approaches from Wellcome Sanger Institute and computational analyses using resources at National Center for Biotechnology Information and European Bioinformatics Institute enable dissection of oncogene-driven heterogeneity. International collaborations such as Human Cell Atlas and infrastructure like European Research Council grants support ongoing mechanistic and translational studies.

Category:Genes Category:Oncology