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Ch. 19 - Epigenetics
Chapter 18, Problem 21

Because the degree of DNA methylation appears to be a relatively reliable genetic marker for some forms of cancer, researchers have explored the possibility of altering DNA methylation as a form of cancer therapy. Initial studies indicate that while hypomethylation suppresses the formation of some tumors, other tumors thrive. Why would one expect different cancers to respond differently to either hypomethylation or hypermethylation therapies?

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1
span>Understand that DNA methylation is a process by which methyl groups are added to the DNA molecule, typically acting to suppress gene expression.</span
span>Recognize that different genes are involved in the development and progression of different types of cancer, and these genes can be affected differently by methylation changes.</span
span>Consider that hypomethylation can lead to the activation of oncogenes, which are genes that have the potential to cause cancer when activated, potentially promoting tumor growth in some cancers.</span
span>Realize that hypermethylation can lead to the silencing of tumor suppressor genes, which normally help prevent uncontrolled cell growth, potentially allowing cancer to develop or progress.</span
span>Conclude that the response of a particular cancer to methylation changes depends on the specific genes involved in that cancer and how they are affected by methylation.</span

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Key Concepts

Here are the essential concepts you must grasp in order to answer the question correctly.

DNA Methylation

DNA methylation is a biochemical process involving the addition of a methyl group to the DNA molecule, typically at cytosine bases. This modification can regulate gene expression without altering the underlying DNA sequence, influencing cellular functions and development. In cancer, abnormal methylation patterns can lead to the silencing of tumor suppressor genes or activation of oncogenes, contributing to tumorigenesis.
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Tumor Heterogeneity

Tumor heterogeneity refers to the diverse genetic and phenotypic variations observed within and between tumors. This variability can arise from differences in genetic mutations, epigenetic modifications, and microenvironmental factors. As a result, different cancer types or even subtypes of the same cancer may respond differently to treatments targeting methylation, making personalized approaches essential in cancer therapy.
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Epigenetic Therapy

Epigenetic therapy involves the use of drugs or interventions to modify epigenetic marks, such as DNA methylation, to restore normal gene function in cancer cells. These therapies can either inhibit methylation (hypomethylation) to reactivate silenced genes or promote methylation (hypermethylation) to silence overactive oncogenes. The effectiveness of these therapies can vary significantly among different cancers due to their unique epigenetic landscapes.
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Related Practice
Textbook Question

Trace the relationship between the methylation status of the glucocorticoid receptor gene and the behavioral response to stress.

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Textbook Question

Prader–Willi syndrome (PWS) is a genetic disorder with a clinical profile of obesity, intellectual disability, and short stature. It can be caused in several ways. Most common is a deletion on the paternal copy of chromosome 15, but it can also be caused by an epigenetic imprinting disorder, and uniparental disomy, an event in which the affected child receives two copies of the maternal chromosome 15. A child with PWS comes to your clinic for a diagnosis of the molecular basis for this condition. The gel below shows the results of testing with short tandem repeats (STRs) from the region of chromosome 15 associated with the disorder.

Is this case caused by a deletion in the paternal copy of chromosome 15? Explain.


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Textbook Question

Prader–Willi syndrome (PWS) is a genetic disorder with a clinical profile of obesity, intellectual disability, and short stature. It can be caused in several ways. Most common is a deletion on the paternal copy of chromosome 15, but it can also be caused by an epigenetic imprinting disorder, and uniparental disomy, an event in which the affected child receives two copies of the maternal chromosome 15. A child with PWS comes to your clinic for a diagnosis of the molecular basis for this condition. The gel below shows the results of testing with short tandem repeats (STRs) from the region of chromosome 15 associated with the disorder.

Based on your interpretation of the data, what is the cause of PWS in this case? Explain your reasoning. 

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Textbook Question

From the data in Table 19.3, draw up a list of histone H3 modifications associated with gene activation. Then draw up a list of H3 modifications associated with repression.

Are there any overlaps on the lists?

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Textbook Question

From the data in Table 19.3, draw up a list of histone H3 modifications associated with gene activation. Then draw up a list of H3 modifications associated with repression.

Are these overlaps explained by different modifications?

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Textbook Question

From the data in Table 19.3, draw up a list of histone H3 modifications associated with gene activation. Then draw up a list of H3 modifications associated with repression.

If not, how can you reconcile these differences?

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