Transformation and Gene Mutations

Pataasin ang iyong marka sa homework at exams ngayon gamit ang Quizwiz!

46. Oncogenes are typically (A) Dominant-acting genes (B) Negative regulators of cell growth (C) The cause of inherited cancers (D) None of the above

A

51. Hereditary nonpolyposis colon cancer has been linked to defects in [Multiple choice] (A) Mismatch repair (B) Base excision repair of guanine oxidation products (C) Nucleotide excision repair (D) DNA double strand break repair (E) None of the above is correct

A

60. Humans deficient in the MutY protein (MYH gene product) are [Multiple choice] (A) Defective in repair of 8-oxo-guanine base pairs with adenine (GO•A base pairs) and prone to colon cancer. (B) Defective in nucleotide excision repair and prone to skin cancer. (C) Defective in double strand break repair and prone to renal cancer. (D) Defective in mismatch repair and prone to pancreatic cancer. (E) None of the above is correct

A

68. Which of the following alterations could give rise to an inherited cancer? [Multiple choice] (A) Loss of a tumor suppressor (B) Activation of an oncogene (C) A and B (D) None of the above

A

71. E2F plays an important role in malignant transformation by [Multiple choice] (A) activating the synthesis of factors involved in DNA replication (B) repressing the function of p53 (C) directly repressing Rb (D) activating p53 which leads to programmed cell death (E) binding the c-myc product and activating Rb gene expression

A

Inheritance of a single copy of a defective MSH2 gene is sufficient to confer cancer predisposition because [multiple choice] A) Only one wild type copy of the MSH2 gene remains, and its inactivation by somatic mutation confers a mismatch repair defect. B) Hereditary nonpolyposis colon cancer occurs only in males and the MSH2 gene is located on the X chromosome. C) MSH2 mutations that have been identified in hereditary nonpolyposis colon cancer families are dominant in the biochemical sense: the protein product of the mutant gene inhibits the mismatch repair reaction that would otherwise be supported by the wild type copy that is also present in diploid somatic cells. D) Since the MSH2 gene product is rate-limiting for mismatch repair, one defective copy of the gene results in a 1000-fold increase in mutation rate even though a second functional copy of the gene is also present. E) None of the above is correct.

A

44. Which of the following would be most likely to give rise to an inherited cancer [Multiple choice] (A) Mutated Ras gene (B) Mutated Rb gene (C) Amplification of the EGFR gene (D) A and B (E) None of the above

B

45. The Her2 gene is an example of: (A) Tumor suppressor (B) Oncogene (C) Inherited cancer gene (D) Oncogene addiction (E) B and C

B

49. You see 100 patients with colorectal cancer, and you and your team determine that 30 of these patients have advanced disease (either local invasion or distant metastases). You believe that the remaining 70 can be cured by surgical resection (removal of the tumor) because no metastatic disease, either local or distant, is detectable with available methods. While the majority of these patients do very well, 15 will die with multiple metastatic sites. What can you conclude about the process of metastasis? (A) If you cannot detect metastases then they are not there (B) Distant metastases may have originated from tumors that do not show evidence of local invasion (C) These distant metastases are most likely due to a second unrelated cancer (D) All of the above are reasonable conclusions (E) None of the above are reasonable conclusions

B

54. What is a property of normal epithelial cells NOT usually found in mesenchymal cells? [Multiple choice] (A) High migration rates (B) Cell polarity (C) The propensity to have two nuclei (D) Extensive cell contact with stromal components (E) High levels of protein secretion

B

64. During most epithelial-mesenchymal transitions the levels of E-cadherin are reduced and this leads to: [Multiple choice] (A) An increase in the number and strength of adherens junctions (B) An increase in the nuclear levels of ß-catenin (C) An increase in the association of ß-catenin and E-cadherin (D) The transactivation of many genes by alpha-catenin. (E) An increase the levels of ZO-1 protein.

B

Cancers can originate in progenitor cells if [multiple choice] A) The progenitor has the ability to give rise to multiple lineages B) The relevant mutation endows progenitor cells with the self renewal properties of a stem cell C) The progenitor is dependent on specific developmental pathways for growth D) A and B

B

How could you explain the so-called "soil and seed" property of cancers that describes the proclivity of some types of cancers (e.g., adenocarcinoma of the prostate) to metastasize to certain distant sites (e.g., bone)? [multiple choice] A) Certain tumor cells will be specifically attracted to the preferred tissue B) Certain tumor cells will only survive in the preferred tissue C) Certain tumor cells will be deterministically sent to the preferred tissue because of anatomical constraints D) All of the above can explain this phenomenon E) None of the above can explain this phenomenon

B

43. Which of the following is NOT an example of activation of an oncogene [Multiple choice] (A) Acquisition of the Src gene by a retrovirus (B) Re-arrangement of the Myc gene with the immunoglobulin enhancer locus (C) Deletion of the Ras gene (D) Deletion of the p16 cyclin kinase inhibitor (E) None of the above

C

48. E2F plays an important role in malignant transformation by: [Multiple choice] (A) repressing the function of p53 (B) directly repressing Rb (C) activating the synthesis of factors involved in DNA replication (D) activating p53 leading to programmed cell death (E) binding the c-myc product and activating Rb gene expression

C

52. In the "seed and soil" hypothesis of Paget, the soil refers to the following: (A) A particular route of metastasis (B) The intrinsic properties of metastatic cancer cells that lead them to home in a specific organ (C) The properties of a particular organ that make it a likely site of metastasis (D) The ability of a small population of cancer stem cells to resist chemotherapy (E) The clonal nature of metastases

C

53. Epithelial-mesenchymal transitions are believed to be essential for: [Multiple choice] (A) The ability of cancer cells to evade apoptosis and thus escape checkpoints mediated by the p53 pathway (B) The activation of telomerase and subsequent immortalization of cancer cells (C) The ability of cancer cells to get past the basement membrane and invade adjacent tissue layers (D) The mutator phenotype (E) The clonal origin of tumors

C

55. In a mesenchymal-epithelial transition, like the ones postulated to occur in metastases of colorectal carcinomas, when the cells become more epithelial you would expect the following: [Multiple choice] (A) a marked decrease of E-cadherin expression (B) movement of beta-catenin from the cytoplasm to the nucleus (C) an increase in the expression of E-cadherin (D) all of the above (E) none of the above

C

58. Deficiency of human Xeroderma pigmentosa C (XPC) (A) Confers a defect in the processing of 8-oxo-guanine lesions and is associated with a high incidence of colon polyps (B) Confers a defect in DNA double-strand break repair, leading to breast cancer. (C) Confers a defect in the nucleotide excision repair of DNA UV damage, leading to skin cancer (D) Confers a defect in the correction of DNA replication errors, which leads to colon cancer.

C

Cancer stem cells may explain why some cancers recur after apparently successful treatment. This type of cell is operationally defined as [multiple choice] A) a stem cell that becomes transformed B) the cells within a cancer that resembles the stem cell of the tissue in which the cancer occurs C) the cell that propagates the tumor D) the cells induced by treatment E) none of the above

C

EMT is almost always mediated by: [multiple choice] A) Mutations that result in deletion of epithelial genes B) Mutations that result in inactivation of epithelial genes C) Changes in gene expression patterns induced by soluble factors D) Periodic changes in gene expression mediated by circadian clocks E) Boring lectures

C

Follicular lymphoma is characterized by a translocation involving chromosomes 14 and 18. What gene is placed under control of the immunoglobulin promoter in this translocation? [multiple choice] A) Mcl-1 B) Bax C) Bcl-2 D) Bcl-6 E) Myc

C

Imagine that you are a pathologist examining the expression of molecular markers in biopsies from a metastatic sarcoma, a tumor of mesenchymal origin, and you find groups of the cancer cells that express E-cadherin on the plasma membrane. Which of the following processes can explain this observation: [multiple choice] A) The sarcoma cells have undergone EMT B) There has been a reversion of the deletion of the E-cadherin genes in a clone of the sarcoma cells C) The sarcoma cells have undergone MET D) Both a and c can explain the observation E) None of the above

C

Inherited cancer genes such as retinoblastoma are typically tumor suppressors. The reason for this is: [multiple choice] A) The tumor suppressor phenotype is carried in a silent state until the second copy of the gene is mutated B) An activated oncogene would likely interfere with normal embryonic development C) All of the above D) None of the above

C

36. Rb is a tumor suppressor. It's normal function is: [Multiple choice] (A) Activating the APC (B) Activating the DNA replication checkpoint (C) Repairing DNA damage (D) inhibiting transcription of S-phase genes (E) blocking entry into G0

D

51. Which process(es) require(s) epithelial-mesenchymal transitions (A) Metastasis during tumor progression (B) Organogenesis during embryogenesis (C) Fibrosis (D) All of the above (E) A and C

D

61. Which of the following statements concerning BRCA1 and BRCA2 is INCORRECT? [Multiple choice] (A) Genetic defects in BRCA1 and BRCA2 have been linked to breast cancer (B) The products of the BRCA1 and BRCA2 genes are believed to play an important role in recombinational repair of double strand breaks. (C) Inheritance of a single defective copy of BRCA1 or BRCA2 is sufficient to confer strong cancer predisposition. (D) BRCA2 defects have been linked to hereditary colon cancer (E) Chromosome breaks and chromosome rearrangements are relatively common in BRCA1 or BRCA2-deficient cells.

D

65. Mesenchymal-epithelial transitions contribute to the formation of macro-metastasis because epithelial cells are: [Multiple choice] (A) Non-motile (B) Capable of invading through basement membranes (C) More adapted to the pressure encountered in arterial blood (D) Capable of forming adherens junctions and other interactions that hold these cells together (E) Divide ten times faster than mesenchymal cells

D

69. Development of an oncogenic activity can result from: [Multiple choice] (A) Single nucleotide mutations (B) Rearrangements that create chimeric proteins (C) Deletions that result in the loss of normal proteins (D) All of the above (E) None of the above

D

72. The Rb pathway is inactivated in: [Multiple choice] (A) Only a small fraction of human cancers (B) Cells in G0 arrest (C) Only in retinoblastoma (D) The majority of human cancers (E) None of the above

D

Rb pathway function is inactivated [multiple choice] A) In only a small fraction of tumors B) Only in retinoblastoma C) Only in inherited retinoblastoma D)In the majority of cancers E) None of the above

D

The challenge in overcoming small gains in cancer survival with new cancer drugs includes: [multiple choice] A) An ability to identify the fraction of patients who benefit from the drug B) An ability to discover new drugs that will be effective in the treatment of all patients of a cancer type (such as breast cancer) C) An ability to generate drug combinations that match the complexity of a patient's tumor D) A and C E) A, B, and C

D

The following are types of trans-acting factors that mediate important regulation during EMT [multiple choice] A) Transcriptional repressors B) Non-coding RNAs C) Alternative splicing factors D) All of the above E) A and C

D

Which of the following are commonly observed in cancer cells? [multiple choice] A) Abnormal chromosome number B) Chromosome rearrangements C) Frequent mutations at the nucleotide level, e.g., base substitution and/or insertion/deletion mutations. D) All of the above are correct. E) None of the above is correct.

D

44. Which of the following is NOT an example of an oncogene activation (A) Mutation of Ras to a state that constantly binds GTP (B) Amplification of the Myc gene (C) Deletion of the retinoblastoma gene (D) Amplification of the p16 cyclin kinase inhibitor (E) C and D

E

46. Changes in the way that individual colon cancer patients respond to an EGFR inhibitor would most likely derive from: [Multiple choice] (A) Acquired mutation in EGFR gene in the tumor (B) Inherited genetic variation that influences immune recognition of the tumor (C) Inherited genetic variation that affects efficiency of drug metabolism (D) Acquired mutation in Ras gene in the tumor (E) A or D

E

47. Variation in individual breast cancer patients with respect to response to cancer drugs and eventual outcome can derive from: (A) Variation in mutations that give rise to the tumor (B) Inherited genetic variation that influences immune recognition of the tumor (C) Inherited genetic variation that affects efficiency of drug metabolism (D) Tumor-stroma interactions that facilitate metastasis (E) All of the above

E

50. Tumor heterogeneity can be caused by (A) The fact that tumors are composed of cancer and non-cancer cells (B) All tumor cells are derived from a single cell (C) All tumor cells have undergone malignant transformation and can form tumors when implanted in nude mice (D) Because of the mutator phenotype there is genetic diversity among cancer cells in a tumor (E) A and D

E

52. The Nowell model postulates that tumor development [Multiple choice] (A) Is an evolutionary process occurring at the cellular level (B) Involves the progressive acquisition of mutations that circumvent growth regulatory control (C) Involves clonal selection for cells with a proliferative advantage (D) Is facilitated by inactivation of genetic stabilization systems (E) All of the above are correct

E

57. In humans, mismatch repair (A) Is important for the correction of DNA replication errors (B) Depends on the products of the MSH2, MSH6, MLH1 and PMS2 genes. (C) Is defective in tumor cells from patients with hereditary nonpolyposis colon cancer (D) Is directed to the new DNA strand at the replication fork (E) All of the above are correct

E

59. The Nowell model postulates that tumor development [Multiple choice] (A) Is an evolutionary process occurring at the cellular level in a tissue. (B) Involves the progressive acquisition of mutations that circumvent growth regulatory control. (C) Involves clonal selection for cells with a proliferative advantage. (D) Is facilitated by inactivation of genetic stabilization systems. (E) All of the above are correct.

E

63. Which of the following tumor cells contribute to metastatic behavior of carcinomas? [Multiple choice] (A) Cancer cells that have undergone epithelial-mesenchymal transitions (B) Cancer cells with epithelial phenotypes (C) Normal cells in tumors (e.g., macrophages) (D) A and B (E) A, B and C

E

66. As cancer cells invade from the mucosal layer deeper into an organ, these cells can be altered by [Multiple choice] (A) Phenotypic changes induced by interactions with stromal components (B) Phenotypic changes induced by growth factors (C) Genetic changes (D) A and B (E) A, B and C

E

70. The following can contribute to malignant transformation: [Multiple choice] (A) Somatic mutations in the tumor cell that activate cell growth (B) Somatic mutations in the tumor cell that inhibit apoptosis (C) Germline mutations that diminish arrest of the cell cycle when DNA is damaged (D) A and B (E) A, B, and C

E

Oncogene activation can result from: [multiple choice] A) Single nucleotide mutations B) Chromosomal rearrangements that create fused proteins C) Amplification or overexpression of a growth factor receptor gene D) Deletion of a growth regulatory gene such as a cyclin kinase E) A, B, C

E

The Nowell model postulates that tumor development [multiple choice] A) Is an evolutionary process occurring at the cellular level in a tissue. B) Involves the progressive acquisition of mutations that circumvent growth regulatory control. C) Involves clonal selection for cells with a proliferative advantage. D) Is facilitated by inactivation of genetic stabilization systems. E) All of the above are correct.

E

Which of the following is (are) an example of an oncogene activation? [multiple choice] A) Mutation of Ras to a state that constantly binds GTP B) Amplification of the Myc gene C) Amplification of the gene encoding the retinoblastoma protein D) All of the above E) A and B

E


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