Broadly categorize the genes involved in tumorigenesis

Broadly categorize the genes involved in tumorigenesis

Each question is worth 16 points.  Your complete answer to each question (this includes all subparts of the question) should be no longer than 2 pages double-spaced.  I will consider your answer complete at the end of the 2nd page and not read beyond this length.   Your exam should be no more than 6 pages in total, outside of the exceptions noted below.

Please cite references (text for this course, original primary literature, and/or review articles) to support your answer. References should follow the reference style of “Uniform Requirements for Manuscripts Submitted to Biomedical Journals” (http://www.nlm.nih.gov/bsd/uniform_requirements.html) and be cited where they are used, not just in a running bibliography at the end of the exam.  References do not count in the page length.  Figures may also be included and do not count in the page length, but must be adequately explained in the text.  Formatting for your document should include 12-point font and 1 inch margins.

2. Genetic basis of cancer

2.) Read the paper by Stehelin, et al. (Nature, 1976) in eReserves.  Prior to this paper, there were three competing hypotheses about the origins of cancer in humans.  Cancer was thought to be directly caused by viral infection, exogenous agents (smoking, pollution, etc.) or in rare cases where there was a family history, a genetic component was acknowledged.  From the results in this paper, the “oncogene hypothesis” was born and we now know “cancer is a genetic disease.”  Explain the key discovery in this paper (8 points) and how this accelerated our understanding of the origins of cancer (8 points).

3. Genes involved in tumorigenesis

a.) How do we broadly categorize the genes involved in tumorigenesis? Compare and contrast these two categories with regard to number of hits to activate/inactivate, types of events leading to activation or inactivation, and functions of proteins encoded by the genes (8 points).

p53 and pRb are two important proteins involved in tumorigenesis.  Please explain:

b.) How each of these proteins works to constrain cell proliferationc.) The physiological stresses or inputs that impact p53 and pRb signaling.

In your explanation also include:

d.) An example of how each protein is activated (molecules upstream) and the downstream consequences of this and converselye.) What inactivates (molecules upstream) the protein and the downstream consequences of the protein being inactivated

(8 pts each for p53 and pRb, 2 pts from each of the four parts).

4. Immortalization

a.) Describe the steps necessary for a cell to become “immortal.”  Include in your description the molecular alterations correlated with the steps in this process.

b.) Based on your knowledge of how the genes involved in cancer become activated and inactivated, describe why the breakage-fusion-breakage cycles could lead to a growth advantage for cells on the path from normal to cancer.

c.) Explain the consequences of these breakage-fusion-breakage cycles on the subsequent population of cancer cells.

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