Biology 205 Genes and Cancer.

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I. Cancer.

A. Explain the distinction between Tumor(neoplasms) and Cancer

• Transformation - Process by which cell growth/development becomes unconstrained
• Cancer - resulting cells can spread to other tissues - metastasis
• Benign (no metastasis) usually not life threatening
• Define oncogenesis p 375

Comment: Note that tumor is any tissue mass that arises from some sort of deviation in the normal program of cell division and may be benign or malignant.

B. Explain the relationship of the cell cycle to cancer.

• Explain how cell division is regulated in normal cells.

Note the existence of two sorts of controls on the cell cycle: growth factors that stimulate cell division and growth inhibiting factors. Cancer in a sense is genetically based disease resulting from mutations coding for growth factors or growth inhibitory factors mutate.

C. Sporadic vs familial cancers...only 1% of cancer cases clearly familial

• Explain the distinction between sporadic and familial cancers.
• Explain the two hit model for retinoblastoma fig 18.4

II. Comments on cancer cells: Cancer cells generally have the following sorts of characteristics:

• Loss of contact inhibition
• Failure to undergo apoptosis
• High levels of telomerase
• Clonal - result from a single cell.
  • Evidenced by expression of only one X chromosome in the cells in a cancer
  • But population of cells becomes genetically heterogeneous due to genetic instability
    • a. mutations, gene amplification, aneuploidy
    • b. selection for cells capable of high proliferation and metastasis
• Most cancers relate to mutations involving control of cell cycle.
• Viewed today as resulting from accumulated mutations...see figure 18.11

III Distinguish between the types of genes involved in cancer

• Oncogenes- gain in function mutations in genes related the regulation of cell division. Table 18.2 gives examples.
  • Result from mutations that cause over expression of a product involved in regulating the cell cycle.
  • Normal unmutated forms of these genes are called proto-oncogenes.
  • Example:Cyclin D/ Cdk4. Excessive production leads to early entry into S phase.
    • Found in 35% of esophageal cancers
    • Amplification of cyclin D gene in 15% of breast cancer but over- expression in 50% of breast cancers!
• Tumor suppressor genes
  • Normally inhibit cell division
  • When inactivated, cell division become uncontrolled. This involves loss of function mutations.
  • Example: Retinoblastoma (p 375-376) note Hereditary Vs Sporadic forms.
    • RB gene on chromosome 13 codes for pRB protein. Table 18.3 gives examples of tumor suppressing genes

     

• Mutator genes: The normal forms of these genes are typically involved in DNA replication and repair. When these genes mutate, they cause mutations in other genes, perhaps in proto-oncogenes and tumor supressor genes. So these genes don't directly cause cancer.

   

  Comment: Figure 18.8 contrasts the effects of mutation in proto-oncogenes and tumor suppressor genes.

   

IV. Genetics of colon cancer

• Illustrates the development of cancer as a multi-step process. See page 388-389.
• Features of colon cancer
  • Requires 5 - 7 mutations in a single cell or cell line
  • Both the order and number of mutations in different genes important
  • Hereditary non-polyp colon cancer caused by mutation in gene related to DNA repair
  • In turn mutations arise in proto-oncogenes and tumor suppresser genes

V. Describe examples of chromosomal rearrangements associated with cancer.

• Extra copies of chromosome 21 in Down's lead to increased Leukemia
• Translocation between chromosome 9 and 22 leads to Philadelphia Syndrome. See pp 442

VI. Describe the major causes of cancer

• At least 50% of al cancers related to environmental factors
• May be synergistic interactions between several factors. Example smoking and radon increase the risk of cancer well beyond the separate risks added together.
• Describe the major environmental causes of cancer
  • Radiation ionizing Vs non ionizing
  • Mutagens often carcinogens
  • Describe the Ames test used to screen for mutagens. p 408 and figure 19.14
  • Diet and behavioral choices:
    • Risk of colon cancer related to intake of animal fat
    • Smoking

VII Viruses and cancer

• Review the Retrovirus multiplication cycle.
  • transducing retroviruses carry oncogenes example Rous sarcoma viruses in chickens. p 378- 379
  • retrovirus virus caused suppression of immune system(HIV) often prevents suppression of cancer cells by immune system
• DNA tumor viruses typically cause cancer cause production of a viral protein that happens to promote host cell DNA product
• DNA virus do not carry oncogenes
• Give examples of DNA tumor viruses. See p 383

11/12/02 pgd

revised 04/16/05