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Introduction to Cancer Biology by Robin Hesketh Study Questions CH04 Introduction to Cancer Biology Robin Hesketh Study Questions CH04 Multiple choice questions (choose the one correct answer from the five choices) Which ONE of the following is a tumour suppressor? a. AKT b. APC c. BCL2 d. KRAS e. MYC Which ONE of the following is present in the Philadelphia chromosome? a. ABL1 b. ACK1 c. AKT1 d. AML1 e. APC Introduction to Cancer Biology | Robin Hesketh |© Cambridge University Press 2013 Introduction to Cancer Biology by Robin Hesketh Study Questions CH04 Which ONE statement about chromosomal translocations is correct? a. Gene disruption occurs but new properties cannot be acquired. b. No loss of genetic material occurs in balanced translocations. c. Translocations are carried by fewer than 1 in 10,000 individuals. d. Translocations cannot be inherited. e. When a translocated chromosome is involved meiosis cannot give rise to a normal gamete. Which ONE of the following statements applies to tumour suppressor genes? a. Li‐Fraumeni syndrome is caused by inactivation of the RB1 gene. b. Mutation in one allele often predisposes carriers to greater inherited cancer susceptibility. c. Mutations exert dominant effects. d. They are activated by many oncogenic DNA viruses. e. They are rarely inactivated in tumours expressing oncogenic RAS. Which statement about transcription of eukaryotic genes is FALSE? a. Almost all transcripts contain 5' and 3' untranslated regions. b. Introns range in size from ~10 nucleotides to >100,000 nucleotides. c. Most exons are ~150 nucleotides long. d. Most human genes are alternatively spliced. e. Ribosomal RNAs do not undergo post‐transcriptional processing. Introduction to Cancer Biology | Robin Hesketh |© Cambridge University Press 2013 Introduction to Cancer Biology by Robin Hesketh Study Questions CH04 Which ONE statement about the origins of cancer is correct? a. Epidemiological studies show that the incidence of cancer is mainly due to hereditary susceptibility factors and not to environmental factors. b. Once stem cells colonise a location from which a tissue will arise they always lose their capacity for self‐renewal. c. Chemical carcinogens cause production of free radical intermediates that form covalent adducts with histone H3 thus exposing genes to excessive transcription. d. Carcinogenesis arises from multiple mutations of a relatively limited set of genes. e. Activation of both alleles of a tumour suppressor gene is required before cancer can develop. Which ONE of the following explains why most newly arising point mutant alleles are recessive? a. The cell recognises the altered DNA sequence as mutant. b. They are less deleterious in heterozygotes than dominant alleles. c. They are less likely to be selected out of the population than dominant alleles. d. They are not usually transcribed. e. They inactivate protein function, and the homologous allele produces a normal protein. Introduction to Cancer Biology | Robin Hesketh |© Cambridge University Press 2013 Introduction to Cancer Biology by Robin Hesketh Study Questions CH04 Which ONE statement is correct for cells in which p53 function has been permanently deleted? a. Cells are less likely to survive double‐strand DNA breaks. b. Cells are more likely to survive double‐strand DNA breaks. c. Cells cannot initiate apoptosis. d. Cells cannot initiate DNA repair. e. Cells cannot sustain normal developmental programmes. Which ONE of the following is NOT normally a characteristic of cancer cells? a. Reduced requirement for glycolysis. b. Reduced requirement for stimulation by growth factors. c. Resistance to apoptosis. d. Resistance to inhibitory growth signals. e. Unlimited replicative capacity. Which ONE of the following is NOT a characteristic of oncogenes? a. A significant number encode protein phosphatases. b. Their gene products function mainly in growth factor signalling pathways. c. They are derived from normal genes. d. They are dominant in their mode of action. e. They are highly conserved between species. Introduction to Cancer Biology | Robin Hesketh |© Cambridge University Press 2013 Introduction to Cancer Biology by Robin Hesketh Study Questions CH04 Which ONE of the following is TRUE of the response to DNA damage? a. Activation of ATM leads to phosphorylation of p53. b. CDC5 inactivates CDK2. c. p53 activates the CDK4/cyclin D complex. d. p53 binds with increased affinity to MDM2. e. The half‐life of p53 is decreased. Essays (approximately one‐hour answers incorporating sketches, graphs and tables as required) 1. Discuss the types of mutation in mitogenic signal transduction pathways that can become oncogenic. 2. How do genetic changes commonly associated with cancers subvert the normal control of mammalian cell proliferation? 3. The retinoblastoma gene (RB1) provides the classical example of the ‘two‐hit theory’ of tumour suppressor/gene inactivation in cancer. With particular reference to RB1, TP53/P53 and VHL, discuss the extent to which other tumour suppressor genes conform to this theory. 4. What are micro RNAs and how might they contribute to the development of cancers? 5. What are the major sources of DNA damage? How do cells repair damaged DNA? 6. Discuss the role of defective DNA repair in causing colon cancer. 7. How has the study of viruses and their genes aided our understanding of carcinogenesis? Introduction to Cancer Biology | Robin Hesketh |© Cambridge University Press 2013 Introduction to Cancer Biology by Robin Hesketh Study Questions CH04 8. How has the study of familial cancer illuminated our understanding of cancer in the general population? 9. What do we know of the mechanisms of genetic instability in human cancer? 10. On the basis of our knowledge of the signalling pathways activated by members of the EGFR family, discuss the role of these receptors in the development of human cancers. 11. How is trans‐membrane signalling achieved by members of the epidermal growth factor family? What is the evidence that members of the EGFR family are involved in the development of human cancers? 12. Discuss the consequences of chromosome rearrangements in cancers. 13. What contributes to genomic instability in cancer cells and what are the implications of such instability for a cancer cell? 14. Discuss the genetic changes associated with the development of human colon cancer. 15. Discuss the role of epigenetic modifications of the genome in cancer. 16. How do defects in DNA repair contribute to cancer? Five‐minute questions (to be answered with notes, sketches, graphs, etc.) 1. Why are some retroviruses tumourigenic agents in appropriate hosts? 2. What are micro RNAs and how are they generated? Introduction to Cancer Biology | Robin Hesketh |© Cambridge University Press 2013