Cancer Biology

• What is the primary cause of genetic instability in cancer cells?

  Defects in the ability to repair DNA damage
• What are the consequences of mutations in cancer cells?

  They lead to changes in DNA sequence and produce rearrangements such as translocations and duplications
• What is another source of chromosome instability in cancer cells?

  Defects during chromosome segregation in mitosis
• What type of mutations do cancer cells contain?

  Somatic mutations
• Why are mutations in cancer cells referred to as somatic?

  Because they occur in body cells, not in the germ line
• What must happen for a single abnormal cell to give rise to a tumor?

  It must pass on its abnormality to its progeny
• What are the types of mutations associated with cancer?

  Oncogenes, tumor suppressor genes, DNA repair genes, genes regulating blood supply, and genes regulating cell adherence
• What is the natural function of oncogenes?

  To promote cell proliferation
• How do cancer cells affect oncogenes?

  They carry gain-of-function activating mutations that foster unregulated cell division
• What does HER-2 oncogene code for?

  A transmembrane protein
• Where is HER-2 expressed?

  On the plasma membrane of all breast glandular cells, especially in breast tissue
• What is the significance of HER-2 overexpression in breast cancer?

  It typically has a worse prognosis due to its positive response to human epidermal growth factor
• What are the scores used to report HER-2 protein expression in breast cancer?

  • 0: Negative (No staining)
  • 1+: Negative (Faint staining in >10% of cells)
  • 2+: Weakly positive (Weak to moderate staining in >10% of cells)
  • 3+: Positive (Strong staining in >10% of cells)
• What is the purpose of HER-2 Fluorescent In Situ Hybridisation (FISH)?

  To detect DNA sequence and identify HER-2 gene amplification or chromosome duplication
• What does a single-colour probe in HER-2 FISH detect?

  HER-2 gene copy number
• What does the dual-colour probe in HER-2 FISH measure?

  One sequence for HER-2 gene amplification and another for chromosome enumeration 17 (CEP 17)
• How is the ratio of HER-2 to CEP 17 used in FISH analysis?

  It defines amplification of the HER-2 gene
• What does a HER-2 to CEP 17 ratio < 1.8 indicate?


  HER-2 gene non-amplification
• What does a HER-2 to CEP 17 ratio > 2.2 indicate?


  HER-2 gene amplification
• What is the role of tumor suppressor genes?

  To keep the behavior of cells under control and suppress inappropriate cell division
• What childhood cancer provided a paradigm for understanding tumor suppressor genes?

  Retinoblastoma
• How do tumor suppressor genes maintain genome integrity?

  By sentencing deviant cells to death by apoptosis
• How are tumor suppressor genes often silenced?

  Epigenetically by methylation
• What is the most common mechanism of silencing tumor suppressor genes?

  Methylation of the promoter
• What effect does the methylated form of cytosine have on base-pairing?

  It has no effect on base-pairing
• What is the role of maintenance methyl transferase?

  It acts on CG sequences that are base-paired with a CG sequence that is already methylated

  
• What happens to methylated CpG sequences during DNA replication?

  The CpG in the newly synthesized strand is initially unmethylated
• How does DNMT1 DNA methyltransferase function?

  It specifically methylates CpG sequences that are paired with methylated CpG
• What are the main targets of oncogenes and tumor suppressor genes?

  • Regulate cell cycle checkpoints
  • Maintain genome integrity
  • Control of the cell cycle is critical for proper functioning
• Why are pathways involved in the control of the cell cycle frequently affected in cancer?

  Because they are critical for a properly functioning multicellular organism
• Cancer is the uncontrolled growth of abnormal cells that can invade nearby tissues or spread to other parts of the body.