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Part III

Dr. Hernandez sits down with Ann and her partner. The doctor is sorry to report that Ann has breast cancer; however, because it was caught early and responds to estrogen and progesterone, the prognosis is good. At this point it looks like the cancer is stage 1. However, as Ann is young, the doctor wants to perform a couple of tests. The first test is a genetic sequencing test for BRCA1 and BRCA2, as well as testing for other genes known to increase the risk of cancer. The other test is an Oncotype DX test on the tumor cells. This is a gene expression test, where the results correlate with how aggressive the cancer cells are. Ann is overwhelmed, but wants to do everything she can to get rid of this disease.

1. As a result of your discussions, you know that mutations in BRCA1 and BRCA2 increase the risk of breast cancer. Because of this, a positive test for these mutations would mean different treatment for Ann, including removal of both her breasts (bilateral mastectomy) as well as her ovaries to prevent ovarian cancer. Ann decides to have the test done, but she is a little hazy on the biology of DNA.

1. Describe the basic structure and function of a gene.
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2. At the molecular level, what is a mutation? Are all mutations harmful? What type of mutation does not lead to a change in protein structure?
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3. The polymerase chain reaction (PCR) is a method that can be used to detect mutations. It uses machinery similar to your cells to replicate a specific DNA sequence, which in this case would be only the mutated gene. Describe the basic process of DNA replication in a cell.
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2. Also, as a result of your discussion, you know that the expression of genes can change in cancerous cells versus noncancerous cells. The Oncotype test will look at the expression levels of several genes in her tumor cells by looking at the mRNA produced.

1. What role does mRNA play in the flow of information in the cell? (Hint: Remember the central dogma of molecular biology.) Please include the basic flow of information in the cell.
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2. Cancer cells and noncancerous cells may have almost identical DNA; however, gene expression can change. Explain the concept of differential gene expression using cancer versus noncancerous cells as an example.
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3. This Oncotype test uses microarray analysis to determine gene expression. Explain to Ann what a microarray is.
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4. The results of Ann’s Oncotype test showed a decrease in the expression of BRCA1. How can this decrease lead to an increase in cell division? (Hint: What is the normal role of BRCA1?)
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3. Both these tests take time and will inform Ann’s treatment plan for the best possible outcome. While she is waiting on results, Ann begins to research the main types of treatments that are available to treat breast (and many other) cancers. One of these is chemotherapy. There are many types of chemotherapy, but in general:

1. How does chemotherapy work?
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2. What are some side effects of chemotherapy?
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3. Based on your knowledge of chemotherapy and cell division, why do you think chemotherapy leads to these side effects?
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Answer 1

Answer a - A gene is a structrual and functional unit of heredity. Genes are made up of DNA. Some genes make mRNA and after transcription form proteins. However many genes do not code for proteins.

Answer b- The term mutation refers to both the change in genetic material and the process by which this change occurs. An organism that exhibits a novel phenotypes resulting from a mutation is called a mutant. Mutation tefers to any sudden, heritable change in the genotype of a cell or an organism. At the molecular level Watson and crick pointed out that structures of the bases in DNA are not static. Hydrogen atom can move from one position in a purine or pyrimidine to another position. Such chemical fluctuations are called tautomeric shift. Mutations resulting from tautomeric shifts in the bases of DNA involve the replacement of purine in one strand of DNA with the other purine and the replacement of pyrimidine with other are called transition.

No all mutations are not harmfull. Because of the degeneracy and order in the genetic code many mutation have no effect on the phenotype of the organism they are called neutral mutations.

Answer a according to the central dogma in molecular biology genetic information flows from DNA to RNA to protein. mRNA codes for protein.