Molecular Basis of Cancer

Question 1

• Properties of malignant cells? (6)
• 4 steps of carcinogenesis?
• 3 gene examples of increasing rates of mutations by hindering DNA repair?
• Types of gene mutations:
  1.) Oncogenes: definition? analogy?
  2.) Tumor supressors: definition? analogy?
• Cytogenetic factors related to malignancy:
  1? Ex? 2? Ex (2)

Answer 1

• Altered morphology, loss of contact inhibition, grow without attachment to solid substrate, proliferate indefinitely, increased saturation density and increased transport of glucose
• Initiation, promotion, conversion, progression
• BRCA1, BRCA2, p53
• Gene that stimulates proliferation is activated, gas pedal
• Inhibit cell proliferation are inactivated, brakes pedal
  1. ) Translocations/deletions; Philadelphia CML
  2. ) LOH loss of heterozygosity = RB and APC

Question 2

• LOH: Final result? Ways it can occur? (4) Supports what theory? Inheritance pattern? Examples of each? (3 each)
• RB: In rapidly proliferating cells? In non-proliferating cells? Represses cells to enter s phase? Tumor supressor? Phosphorylated by? Effect? Target of this kind of cancer?

Tumor supressors:

1. ) APC: Encodes what? Defective APC leads to? Prominant in what types of cancer?
2. ) BRCA 1/2: Type of repair?
3. ) p53: Initially thought to be? How many mutant alleles needed to mess it up (tertramer)?

Answer 2

• Loss of tumor suppressor; mutation, mitotic recombination, chromosome loss, environmental factors; Knudosons 2 hit; AD (Rb, BRCA, Wilms) or AR (XP, AT, FA)
• Hyperphosphoylated; hypophosphorylated; hypo; yes; CDK; inactivate RB; HPV
• Cytoplasmic protein that regulates localization of B - catenin; Arm/B- Catenin to enter nucleus as TF via Wht-APC pathway; colon
• DNA repair
• Oncogene; 1

Question 3

• Way to identify oncogenes?
• Retrovirus examples of oncogene? (2)
• Oncogenes change what of protein?
• Mutation related to receptor protein kinase?
• Oncogenes as diagnosis and prognosis: Bladder cancer example? C-onc genes? erbB2 (protein kinase)?
• How do heat maps work? Ex?
• Breast cancer therapy example?

Answer 3

• Place cells on agar and see if the grow without support
• Virus reverse transcribes near c-SRC which is added to virus transcription and increases activity, G-onc –> V-onc
• quality and quantity
• Normal = GF binds –> tyrosine kinase domain activated, but viral is ligand independent
• Bladder: C-ras is mutated = poor prognosis
• C-onc = N-MYC is found for neuroblastoma
• amplified in 20% of breast cancers (bad prog)
• Gene copy number correlated with tumor grade
  Red = amplified (Oncogenes)
  Blue = Reduced (TS)
• Increased estrogen receptor = Tamoxifin; High ERB2 = Herceptin treatment (Antibody)