Genetics: From Genes to Genomes
6th Edition
ISBN: 9781259700903
Author: Leland Hartwell Dr., Michael L. Goldberg Professor Dr., Janice Fischer, Leroy Hood Dr.
Publisher: McGraw-Hill Education
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Chapter 20, Problem 28P
Glioblastoma multiforme (GBM) is the most common and aggressive form of brain cancer in humans. Withoutany treatment, the mean survival rate is about three months. Even with standard treatments such as surgical resection, radiation, and chemotherapy, the mean survival rate is between seven and 14 months. GBM tumors differ in their spectrum of genetic changes, and these changes may influence the effect of particular treatments. Answer the following questions about the relevance of particular mutations to particular treatments and outcomes.
| a. | Biopsies of about 20% of GBMs show the expression of a certain mutational variant ofthe EGFR (epidermal growth factor receptor) protein called EGFRvIII. The same cancerous cells of these GBMs also show the expression of normal, wild-type EGFR. Is the gene encoding EGFR a tumor-suppressor gene or a protooncogene? |
| b. | It is very difficult to induce cells expressing EGFRvIII to undergo apoptosis. If you were a radiologist treating a patient with a GBM that expresses EGFRvIII, would you use a higher or lower dose of X-rays than with patients having GBMs with normal EGFR proteins? |
| c. | EGFR is a protein that extends through the cell membrane, with an N-terminal extracellular part (amino acids 1–500) that binds epidermal growth factor (EGF) and an intracellular C-terminal kinase part (amino acids 501–1000) that is normally activated when EGF binds to EGFR. The active kinase phosphorylates (adds phosphate groups to) other proteins, setting off a signal transduction cascade that promotes cell growth and division. EGFRvIII is a deletion that removes amino acids 6 through 273 of the EGFR protein. How might this mutant protein contribute to cancer? |
| d. | IressaTM is a drug that blocks the kinase activity of EGFR. Would you expect IressaTM to be a potential treatment for GBMs expressing EGFRvIII, or would you instead anticipate the drug would make the tumors grow faster? |
| e. | Cisplatin is a platinum compound that binds to DNA and damages it, eventually leading to cell death. ERCC1 is a gene that encodes a DNA repair protein. GBMs are found that show much higher levels of transcription of ERCC1 than normal. Would you treat patients having such GBMs with higher or lower doses of cisplatin than patients whose tumors have normal amounts of ERCC1 mRNAs? |
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: The effects of DNA mutations within the p53 gene on the structure and function of the protein encoded by the gene.
The essay should focus on the following discussion points:
The normal functions of the p53 gene.
Known mutations of the gene.
The impact of mutations on the structure of the protein encoded by the gene.
The impact of mutations on the function of the protein.
Current therapeutic interventions that aim to address the impact of mutations on gene function
https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=TP73
using the above linke, Briefly describe the most common mutation found in this gene. Include details about the type of mutation, and the predicted effect. . where does the mutation occur, what bases are changed; does the mutation change the protein sequence, and if so what would the likely biologics consequences be?
Find non-cancerous, non--nonsense, point mutation genetic disease.
Describe the disease's name and the type of mutation.
Compare the gene sequence between wild type and mutant.
Compare the polypeptide sequence and structure encoded by the wild type's gene
and the mutant's gene.
Describe and explain the consequences of the mutation to a patient's health.
Note:
1. These questions will test the concepts of DNA-Protein transcription and
translation on the effects of mutation.
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Chapter 20 Solutions
Genetics: From Genes to Genomes
Ch. 20 - For each of the terms in the left column, choose...Ch. 20 - Characterize the differences between tumor cells...Ch. 20 - Prob. 3PCh. 20 - Prob. 4PCh. 20 - A carcinogenic compound is placed on the skin of...Ch. 20 - You have decided to study genetic factors...Ch. 20 - B cells are specialized blood cells that secrete...Ch. 20 - Molecules outside and inside the cell regulate the...Ch. 20 - Put the following steps in the correct ordered...Ch. 20 - a. Would you expect a cell to continue or to stop...
Ch. 20 - Two different protein complexes called SCF and APC...Ch. 20 - One of the hallmarks of mitotic anaphase is the...Ch. 20 - Concerning the Tools of Genetics Box Analysis of...Ch. 20 - Are genome and karyotype instabilities...Ch. 20 - Prob. 15PCh. 20 - Why dont all loss-of-function mutations that are...Ch. 20 - Chromothripsis is a rare phenomenon, first...Ch. 20 - The chromosome 9/22 translocation associated with...Ch. 20 - A female patient 19 years old, whose symptoms are...Ch. 20 - Prob. 20PCh. 20 - A generic signaling cascade is shown in the...Ch. 20 - Neurofibromatosis type 1 NF1; also known as von...Ch. 20 - Families with germ-line BRCA1 or BRCA2...Ch. 20 - The text explained that retroviruses can cause...Ch. 20 - Hepatocellular carcinoma is the most frequent form...Ch. 20 - Suppose that instead of microarrays, you analyzed...Ch. 20 - Prob. 27PCh. 20 - Glioblastoma multiforme GBM is the most common and...Ch. 20 - a. The legend to Fig. 20.29 identifies which of...Ch. 20 - The website CBioPortal http://www.cbioportal.org...
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- A region on chromosome 6 has been linked to schizophrenia, but researchers have not found a specific gene associated with this disease. What steps would be necessary to locate the gene?arrow_forwardAlthough it is well known that X-rays cause mutations, they are routinely used to diagnose medical problems, including potential tumors, broken bones, and dental cavities. Why is this done? What precautions need to be taken?arrow_forwardWhat is the definition of Driver Mutations & Passenger Mutations? Also describe why each are informative in characterizing tumors.arrow_forward
- To further understand PSEN2 mutations the age of onset of Alzheimer's Disease and AB 42/40 ration is investigated for different mutations in PSEN2. Table 3 - Age at onset of FAD and measured Aß 42/40 ratios for each patient. PSEN2 Mutation Age at onset (Years) AB 42/40 ratio PSEN2 WT Select one: True False N/A 1 1229F M223L F237P M233V F237L N410Y 33 7.3+ 0.7 46 35 3.81 32 4.5 0.2 0.4 14.7 52 31 2.2 ± 1.2 1.8 20.76 + Question 18) Very early onset PSEN2 mutations have a more severe impact on the AB 42/40 ratios than mutations that cause onset at a later age?arrow_forwardDefine a Point mutation and give an example. What is sickle cell anemia and what causes it. What is nondisjunction? How does nondisjunction cause disorders? NUMER YOUR ANSWERSarrow_forwardGene mutations can be classified in two major ways:(1) hereditary or germline mutations that are inherited from a parent and are present throughout a person’s life in virtually every cell in the body.(2) acquired or somatic mutations that occur at some time during a person’s life and are present only in certain cells, not in every cell in the body.If there is no family history of a particular disease but a child has the disease then it may have arisen due to a(n) ________ mutation early during development. A) acquired B) inherited C) silent D) transitionarrow_forward
- The C-myc gene is a proto-oncogene which is highly expressed in breast tissue and appears to cause proliferation of breast tissue and its elevated expression is associated with breast cancer. Based just on the ChIP data from the previous questions (also shown below), which of the three drugs (estrogen, tamoxifen and raloxifene) would you recommend for treating breast cancer? Justify your response and explain the potential side effects of each drug.arrow_forwardName two ways in which loss of p53 function contributes to a malignant phenotype. Explain how benzo(a) pyrene can cause loss of p53 function. Hint: Loss of p53 function occurs in the majority of human tumors.arrow_forwardNeurofibromatosis type 1 (NF1) is an inherited is an inheritent dominant disorder. The phenotype usually involves the production of many skin neurofibromas. Answer the following questions about the disorder: a) Are the NF1 neurofibromatosis-causing mutations that are inherited by affected children from affected parents likely to be loss-of-function or gain-of-function mutations? b) Neurofibromin, the protein product of NF1, is associated with the Ras protein. Ras is involved in the transduction of extracellular signals from growth factors. The active form of Ras is complexed with GTP; the inactive form is complexed with GDP. Would the wild-type neurofibromin protein favor the formation of Ras-GTP or Ras-GDP? c) Which of the following events in a normal cell from an individual inheriting a neurofibromatosis-causing allele could cause the descendents of that cell to turn into a neurofibroma? i. A second point mutation in…arrow_forward
- Which of the following statements are true about the rate of mutation in tumor cells (select all that apply)? A. Mutation rate of tumor cells is reduced compared to normal cells of the same tissue type B. Mutation rate of tumor cells is unchanged compared to normal cells of the same tissue type C. Mutation rate in tumor cells is higher compared to normal cells of the same tissue type D. Affected by genome instability within the tumor cellsarrow_forwardIn Metastatic Breast Cancer [such as in Breast Invasive Ductal Carcinoma; Breast Invasive Carcinoma, NOS; Breast Invasive Cancer, NOS; Invasive Breast Carcinoma; Breast Invasive Lobular Carcinoma; Breast Mixed Ductal and Lobular Carcinoma] what role does the genes Tp53 and Tp63 have? Would one of them affect the other (i.e. mutation, etc) or there is not relationship among the two genes at all.arrow_forwardWhile a stem cell transplant from an unaffected donor is currently the only cure for DBA, genome-editing technologies may one day enable the correction of a mutation in a patient’s own bone marrow stem cells. However, what specific information would be needed, beyond a symptom-based diagnosis of DBA, in order to accomplish this?arrow_forward
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