Oncogenes and Cancer

  1. Oncogene Activation Mechanisms
    1. Definition of Oncogenes
      1. Mutated Proto-Oncogenes
        1. Overexpressed Proto-Oncogenes
          1. Gain-of-Function Concept
          2. Dominant Nature of Oncogenic Mutations
            1. Single Allele Sufficiency
              1. Contrast with Tumor Suppressors
              2. Point Mutations
                1. Structural Alterations
                  1. Functional Consequences
                    1. Constitutive Activation
                      1. Examples in Ras Proteins
                      2. Gene Amplification
                        1. Increased Gene Copy Number
                          1. Protein Overproduction
                            1. Homogeneously Staining Regions
                              1. Double Minutes
                                1. Extrachromosomal DNA
                                2. Chromosomal Translocations
                                  1. Fusion Gene Formation
                                    1. BCR-ABL Example
                                      1. Mechanism of Formation
                                      2. Promoter Swapping
                                        1. Transcriptional Activation
                                          1. Immunoglobulin Gene Rearrangements
                                        2. Insertional Mutagenesis
                                          1. Viral Integration
                                            1. Promoter/Enhancer Insertion
                                              1. Retroviral Activation Mechanisms
                                              2. Epigenetic Alterations
                                                1. DNA Methylation Changes
                                                  1. Histone Modifications
                                                    1. Chromatin Remodeling

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                                                  4. Proto-Oncogenes: Normal Cellular Functions

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                                                  6. Major Oncogene Families