CASE STUDY : When a gene that turns off is a matter of life or death. Jordan is
ID: 278635 • Letter: C
Question
CASE STUDY: When a gene that turns off is a matter of life or death. Jordan is about to start college when he learned he had a brain tumor, specifically a glioblastoma. One possible treatment is a drug called temozolomide, which damages actively dividing cells. But, this drug works more effectively in patients with a particular epigenetic marker on the gene MGMT (O-6-methylguanine-DNA methyltransferase. The MGMT gene encodes a protein that is involved in the repair of DNA. When MGMT cytosine near the promoter region are methylated, the gene is turned off and therefore the DNA in the cancer cells damaged by temozolomide doesn’t get repaired. As a consequence, the cancer cells undergo apoptosis, and thus, the drug can more successfully kill the cancer cells. However, when the MGMT promoter is unmethylated, the gene is turned on and the protein synthesized repairs the DNA of the cancer cells damaged by temozolomide, rendering the treatment ineffective because the targeted cancer cells do not die by apoptosis.
7 - Based on the information provided, is it more favorable for Jordan to have methylated or unmethylated MGMT promoters? Explain why. If Jordan had an identical twin, what is the likelihood that his brother would also develop this cancer?
9 - Examine Figure 1 and describe based on the graphical results the best hypothetical treatment for Jordan if his MGMT promoter is unmethylated.
E 100 Unmethylated radiotherapy 90 80 un 70 60 50 Unmethylated radiotherapy plus temozolomide Methylated. radiotherapy Methylated, radiotherapy plus temozolomide 30 P-0007 20 -0.06 L 6 12 18 30 36 42 Months Fiqure 1. Treatment of Glioblastoma as Related to Overall Survival. From e New England Journal of Medicine, Heqi, M.E. et al., MGMT gene silencing and benefit from temozolomide in glioblastoma, 352, 997-1003, Figure 3A. Copyright C 2005 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society 2 9 6Explanation / Answer
Answer : methylated MGMT promoter should be more favourable for Jordan.
Methylated promoter has more specific activity towards cells. the drug kills the cancer cells so the patient can live longer.
Even if Jordan had an identical twin itvis not mandatory that he will also develop cancer since the gene activity might be proper in his case.
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Jordan has to take the drug temozolomide and along with that chemotherapy to kill and deactivate the cell proliferation. The blue graph is the best treatment if MGMT promoter is unmethylated. Since the patient can live longer in this case .
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