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Ch. 24 - Cancer Genetics

Chapter 23, Problem 24

As part of a cancer research project, you have discovered a gene that is mutated in many metastatic tumors. After determining the DNA sequence of this gene, you compare the sequence with those of other genes in the human genome sequence database. Your gene appears to code for an amino acid sequence that resembles sequences found in some serine proteases. Conjecture how your new gene might contribute to the development of highly invasive cancers.

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Hi everybody. Let's take a look at this practice problem together. Which of the following phrases best describes how genes play a role in invasive cancer. Recall that invasive cancer is cancer cells that are spreading beyond the sight of origination. So, let's take a look at our options. We've got a a single gene mutation is always sufficient to result in invasive cancer. This is a false statement. Typically it is multiple mutations in multiple genes accumulated over time. Single mutation may increase the likelihood of getting cancer, but by itself is usually not enough to cause cancer. Next, we're going to take a look at see gene mutations are only important in the early stages of cancer formation and are unimportant and invasive cancer. This is also an incorrect statement. Gene mutations are important in the early stages of cancer formation and are important in invasive cancer and this is by contributing to cell spreading. Now let's take a look at de invasive cancer is caused by mutations in non coding regions of the genome rather than encoding regions. So this is also a false statement, mutations that cause invasive cancer can occur in both coding and non coding. An example of this is a proto uncle gene that codes for molecules involved in normal cell growth. If mutated, it can become an uncle gene and potentially cause cancer. So D is also incorrect. So our answer therefore has to be B option B. A combination of genetic and environmental variables contributes to the development of invasive cancer. We already know that mutations contribute to invasive cancer, but environmental factors do as well. An example of this is tobacco smoking. It's an environmental factor that can lead to DNA damage and cause invasive cancer. Therefore, B is the correct answer. Alright, everybody. I hope you found this helpful, and I'll see you soon for the next practice problem.
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Radiotherapy (treatment with ionizing radiation) is one of the most effective current cancer treatments. It works by damaging DNA and other cellular components. In which ways could radiotherapy control or cure cancer, and why does radiotherapy often have significant side effects?

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Genetic tests that detect mutations in the BRCA1 and BRCA2 tumor-suppressor genes are widely available. These tests reveal a number of mutations in these genes—mutations that have been linked to familial breast cancer. Assume that a young woman in a suspected breast cancer family takes the BRCA1 and BRCA2 genetic tests and receives negative results. That is, she does not test positive for the mutant alleles of BRCA1 or BRCA2. Can she consider herself free of risk for breast cancer?

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Explain the apparent paradox that both hypermethylation and hypomethylation of DNA are often found in the same cancer cell.

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Mutations in tumor-suppressor genes are associated with many types of cancers. In addition, epigenetic changes (such as DNA methylation) of tumor-suppressor genes are also associated with tumorigenesis [Otani et al. (2013). Expert Rev Mol Diagn 13:445–455].

Knowing that tumors release free DNA into certain surrounding body fluids through necrosis and apoptosis Kloten et al. [(2013). Breast Cancer Res. 15(1):R4] outline an experimental protocol for using human blood as a biomarker for cancer and as a method for monitoring the progression of cancer in an individual.

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Mutations in tumor-suppressor genes are associated with many types of cancers. In addition, epigenetic changes (such as DNA methylation) of tumor-suppressor genes are also associated with tumorigenesis [Otani et al. (2013). Expert Rev Mol Diagn 13:445–455].

How might hypermethylation of the TP53 gene promoter influence tumorigenesis?

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A study by Bose and colleagues [(1998). Blood 92:3362–3367] and a previous study by Biernaux and others [(1996). Bone Marrow Transplant 17:(Suppl. 3) S45–S47] showed that BCR-ABL fusion gene transcripts can be detected in 25 to 30 percent of healthy adults who do not develop chronic myelogenous leukemia (CML). Explain how these individuals can carry a fusion gene that is transcriptionally active and yet do not develop CML.

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