genetic cancer

• Cancer is genetic, but not usually inherited.
• The exact causes of many types of cancer are NOT FULLY understood.
• While extensive research has been conducted on cancer, there are still various aspects of its development that remain unclear.
• Oncogenes and tumor suppressors

  When mutant, can cause cancer
• Cancer cells have different gene expression profiles compared to the cells from which they descend.
• Cancer is caused by a loss of cell division control.
• Implicated genes in cancer

  • Growth factors
  • Transcription factors
  • Telomerase
• Germline mutation


  The change occurs during DNA replication before meiosis, affecting all cells in the body.
• Somatic mutation


  The change occurs during DNA replication before mitosis, affecting only the cells that descend from the original changed cell.
• Cancer susceptibility is directly passed to future generations.
• Cancer susceptibility is not directly passed to future generations; most cancers are sporadic.
• Characteristics of cancer cells

  • Oilier
  • Less adherent
  • Loss of cell cycle control
  • Heritable
  • Transplantable
  • Lack contact inhibition
  • Dedifferentiated
  • Increased mutation rate
  • Induce local blood vessel formation (angiogenesis)
  • Invasive
  • Metastasize
• Steps in the development of cancer

  1. Angiogenesis

  2. Apoptosis

  3. Cell adhesion

  4. Cell cycle control

  5. DNA repair

  6. Signal transduction
• Angiogenesis


  The formation of blood vessels from existing vasculature; a fundamental step in tumor transition from benign to malignant.
• Angiogenesis inhibitors are used in the treatment of cancer.
• Hereditary mutations


  Gene defects passed from parent to child, present in the egg or sperm during fertilization.
• A hereditary mutation is a major factor in about 5% to 10% of all cancers.
• Most cancers are caused by DNA changes that happen during the person's life, called acquired, sporadic, or somatic mutations.
• An acquired mutation can be caused by environmental factors such as exposure to radiation or toxins.
• Knudson Hypothesis

  Cancer is the result of accumulated mutations to a cell's DNA.
• Mutations in the Knudson Hypothesis include one mutation in germline and one mutation in somatic.
• Knudson performed a statistical analysis on cases of retinoblastoma.
• Knudson suggested that multiple "hits" to DNA were necessary to cause cancer.


  1971
• Oncogenes


  Proto-oncogenes are the "good" genes that control cell type and division frequency; mutations can turn them into "bad" oncogenes.
• A few cancer syndromes are caused by inherited mutations of proto-oncogenes.
• Examples of cancer syndromes caused by inherited mutations

  • Multiple endocrine neoplasia type 2 (RET)
  • Hereditary gastrointestinal stromal tumors (KIT)
  • Hereditary papillary renal cancer (MET)
• Most cancer-causing mutations involving oncogenes are acquired, not inherited.
• Chromosome rearrangements, gene duplication, or other mutations generally activate oncogenes.
• Philadelphia translocation is associated with chronic myelogenous leukemia (CML).
• BCR-ABL gene

  Product of Philadelphia translocation that promotes cellular proliferation and suppresses apoptosis.
• Burkitt lymphoma results from chromosome translocations involving the Myc gene.
• Tumor suppressor genes

  Normal genes involved in cell division, DNA repair, or apoptosis.
• Mutated tumor suppressor genes lead to uncontrolled cell growth, which can cause cancer.
• Inherited abnormalities of tumor suppressor genes can cause certain types of cancer to run in families.
• A defective APC gene causes familial adenomatous polyposis, leading to colon cancer.
• Acquired mutations of tumor suppressor genes have been found in many cancers.
• Abnormalities of the TP53 gene have been found in more than half of human cancers.
• p53 protein


  Involved in the pathway to apoptosis; activated when a cell has irreparable DNA damage.
• If the gene for p53 is not functioning properly, cells with damaged DNA continue to grow and divide, leading to cancer.
• In humans, each telomere consists of many repeats of the TTAGGG sequence.