Figure 1. Chromosome translocation. (a) The reciprocal translocation between chromosomes 8 and 14 observed in many patients with Burkitt lymphoma. The MYC locus on chromosome 8 is translocated to chromosome 14, where it becomes constituently expressed under the promoter of the immunoglobulin H (IgH) gene. (b) Genetic rearrangement introduced by the reciprocal translocation between chromosomes 8 and 14 seen in many patients with Burkitt lymphoma. Again, the MYC gene undergoes enhanced transcription by coming under control of the IgH enhancer/promoter apparatus. Note: the genes are represented in parts – enhancers that determine when (?), where and how much ($) a gene is transcribed); promoters (which initiate transcription); the coding region and the termination codon (that ends transcription). (Reproduced with permission from Anticancer Research (1999) 19: 4729–4746.)

Figure 2. Chromosome amplification. (a) Segments of DNA are amplified in tandem arrays and excised as double minutes. These double minutes can be maintained through constant cell selection or reintegrated into the chromosome as an inheritable homogeneous staining region. (b) Genetic rearrangement introduced by the amplification of the EGFR coding region schematic. (See the legend note in Figure 1 for a description of the gene schematic). At the genetic level, multiple copies of a gene are under the same enhancer/promoter apparatus control. The result is the production of multiple transcript copies rather than a single copy. (Reproduced with permission from Anticancer Research (1999) 19: 4729–4746.)

Figure 3. Growth factors. These stimulate (or inhibit) cells through multiple regulatory loops. A cell can stimulate itself through an autocrine (extracellular) or intracrine (intracellular) mechanism. Neighboring cells can be stimulated in a paracrine (through a mature growth factor) or juxtacrine (through a growth factor precursor) fashion. (Reproduced with permission from Anticancer Research (1999) 19: 4729–4746.)

Figure 4. Growth factor receptors. (a) Normal cells are usually activated through binding of an extracellular ligand, such as growth factors. (b) Many cancer cells contain growth factor receptor oncogenes that are activated by: (1) production of an exaggerated number of receptor copies or (2) production of a truncated receptor which transmits a signal independent of receptor–ligand binding. (Reproduced with permission from Anticancer Research (1999) 19: 4729–4746.)

Figure 5. Intracellular messengers. Many oncogenes are mutated intracellular messengers. (a) Under normal conditions, Ras is activated by binding to GTP. This binding is mediated by guanine nucleotide exchange factors (GEF) and inhibited by GTPase activating proteins (GAP). (b) In tumor cells, Ras can be overactivated by overactivity of GEF (usually by a point mutation in Ras itself) or inactivation of GAP. (Reproduced with permission from Anticancer Research (1999) 19: 4729–4746.)

Figure 6. Transcription factors. These determine the genetic response of a cell. Varying combinations of transcription factors determine the activation or repression of response genes. For example, Myc and Max frequently activate gene transcription. However, Max–Max homodimers or Mad–Max heterodimers lead to repression of gene transcription. In tumors over expressing Myc, available Max is sequestered and gene transcription is enhanced. (Reproduced with permission from Anticancer Research (1999) 19: 4729–4746.)