Merrick had been suffering from worsening headaches, nausea and vomiting, and extreme fatigue for several weeks. He was also having trouble with his vision. His doctor ran various tests and gave him a referral for an MRI. When the MRI results came back, the news was not good. Merrick had a tumour.

A biopsy of the tumour was taken to determine whether it was benign or malignant. The results identified that Merrick had Stage IV glioblastoma multiforme, an aggressive cancer of the brain. Glioblastomas are cancers that often spread quickly to other parts of the brain, and it is hard for surgeons to be able to fully remove them. The doctors determined that they would perform surgery and attempt to remove the tumour. The surgeons were able to remove some of the cancer cells, but not all of them—it appeared some had spread. Merrick’s oncologist indicated that Merrick would need to undergo adjuvant chemotherapy as well as radiotherapy, and that they would monitor him to see how his body responded. One particular drug he would take was temozolomide. This drug damages actively dividing cells. Temozolomide works in most but not all patients with glioblastoma. An individual’s epigenetic markers (methylated cytosines or unmethylated cytosines) on the promoter region of a particular gene, MGMT (O-6-methylguanine-DNA methyltransferase), are associated with the effectiveness of temozolomide. MGMT encodes an enzyme which repairs damage to DNA.

1. Given the trouble with Merrick’s vision, on what part of the brain do you think the tumour was located?
2. What is the difference between a benign and malignant tumour?
3. In what cell type do glioblastomas occur? What is the role of this cell type?
4. How does Temozolomide result in the death of cells?
5. The effectiveness of Temozolomide is influenced by the methylation state of MGMT. Study the following graph. How does the methylation of the MGMT promoter relate to the survival of glioblastoma patients?

Figure 1. Survival percentage of glioblastoma patients with methylated vs non-methylated MGMT promoter

6. What role does MGMT play in cancer cell regulation?
7. Which methylation state of MGMT is more favourable for Merrick’s chance of survival?
8. How does methylation impact the effectiveness of Temozolimide?
9. Merrick’s MGMT promoters are methylated. Study the figure below and state which treatment you believe to be the best approach for Merrick. Explain why this approach is the best.

  

Transcribed Image Text:

Probability of Overall Survival (%) 100- 90- 80- 70- 60- 50 40- 30- 20- 10- 0+ 0 Unmethylated MGMT promoter P<0.001 T 6 12 18 24 Months 30 Methylated MGMT promoter 36 42 Probability of Overall Survival (%) 100- 90- 80- 70- 60- 50 40- 30- 20- 10- 0+ 0 Unmethylated MGMT promoter P<0.001 T 6 12 18 24 Months 30 Methylated MGMT promoter 36 42

Answer rating: 100% (QA)

Given the trouble with Merricks vision on what part of the brain do you think the tumour was located The tumour could be located in the occipital lobe ... View the full answer