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For each of the following cancers, describe the gene(s) that have a role in the disease. Explain what class of cancer gene is mutant and how its expression has been changed.

(a) Li-­Fraumeni syndrome.

(b) Chronic myeloid leukemia.

(c) Xeroderma pigmentosum.

(d)Burkitt’s lymphoma.

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Jean Keeling
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27 Jun 2018
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Related questions

The Myc gene is a very important proto-oncogene that encodes the Myc transcription factor. The Myc gene is normally only expressed in response to the presence of growth factors, and once expressed the Myc protein promotes passage through the restriction point by activating the transcription of early cell cycle genes. As an indication of the importance of Myc, overexpression of the Myc protein is sufficient to cause tumorigenesis in many cell types. For example, Burkitt’s lymphoma is the result of a chromosomal translocation that leads to increased myc expression in B-lymphocytes.

(A) (3 pts) What is the restriction point, and which CDK complex is most directly activated by passage through the restriction point?

(B) (10 pts) Describe how activation of the CDK complex from part (A) leads to entry of cells into S-phase. Your answer must indicate the protein(s) that this CDK directly acts on, the proteins that directly stimulate S-phase entry, and the mechanism that prevents premature entry into S-phase.

(C) (8 pts) Indicate whether each protein you mention in part (B) is a proto-oncoprotein (e.g. a protein encoded by a proto-oncogene) or a tumor suppressor. You can incorporate this into your answer to part (B) if you choose.

(D) (4 pts) Why does the overexpression of Myc lead to cancer, for example Burkitt’s lymphoma?

QUESTION 1

  1. The first person to describe a carcinogen was:

    a.

    Rudolf Virchow
    b.

    Cladius Regaud
    c.

    Percivall Pott
    d.

    George Papanicolau
    e.

    Sidney Farber

QUESTION 2

  1. Who introduced the test for early detection of cervical cancerin 1942?

    a.

    Rudolf Virchow
    b.

    Cladius Regaud
    c.

    Percivall Pott
    d.

    George Papanicolau
    e.

    Sidney Farber

QUESTION 3

  1. All of the following are TRUE about risk factors for cancerEXCEPT:

    a.

    They cause DNA mutation
    b.

    Some can be avoided
    c.

    Some can be inherited
    d.

    They guide patient management
    e.

    They increase the probability of getting cancer

QUESTION 4

  1. All of the following are proven carcinogens EXCEPT:

    a.

    Tobacco
    b.

    Formaldehyde
    c.

    Soot
    d.

    Saccharin
    e.

    Human papilloma virus

QUESTION 5

  1. Which of the following is true about somatic mutations:

    a.

    They are present in an egg or sperm
    b.

    They can be inherited
    c.

    They can be present in all cells in the individual
    d.

    They can cause cancer family syndrome
    e.

    They cannot be inherited

QUESTION 6

  1. All of the following can be used as a guideline for causalinference of a carcinogen EXCEPT:

    a.

    Strength of association of the exposure with occurrence ofcancer
    b.

    Single correlation study showing exposure with the incidence ofcancer
    c.

    Dose response relation of the exposure and risk of cancer
    d.

    Disease or risk reduction with removal of exposure
    e.

    Biological plausibility of the exposure with the disease

QUESTION 7

  1. All of the following cancers have an infectious causeEXCEPT:

    a.

    Cervical Cancer
    b.

    Stomach Cancer
    c.

    Breast Cancer
    d.

    Liver Cancer
    e.

    Hodgkin lymphoma

QUESTION 8

  1. Medical treatments that cause cancer include all of thefollowing EXCEPT:

    a.

    MOPP chemotherapy for Hodgkin lymphoma
    b.

    Radiation therapy for sarcoma
    c.

    Tamoxifen for chemotherapy
    d.

    Smallpox vaccination
    e.

    Cyclosporine for immunosuppression

QUESTION 9

  1. All of the following are risk factors for breast cancerEXCEPT:

    a.

    Having breast implants
    b.

    Having prior ovarian cancer
    c.

    Having a mother with breast cancer
    d.

    Age
    e.

    Obesity

QUESTION 10

  1. The likelihood of getting cancer from exposure to a carcinogenis related to all of the following EXCEPT:

    a.

    The duration of exposure
    b.

    The geographic location of the exposure
    c.

    The degree of exposure
    d.

    The genetic susceptibility of the exposed person
    e.

    The mode of exposure (e.g., touching it, breathing it,swallowing it, etc).

It was all over the news this morning (March 29, 2018) that a new cancer “vaccine” was about to begin human trials after a 97% success rate in mouse trials against both blood cancers (lymphomas) and solid tumors such as breast and colon cancer. I will excerpt a description compiled from several scientific and news sources. Based on what we talked about in Bio 221, you should be able to understand this. Answer each of the questions about this exciting new “vaccine.”

T cells are present in most tumors by infiltration. These include CTLA4-expressing Treg cells, as well as CD4- expressing TH cells and CD8-expressing cytotoxic T-lymphocytes. Once cancer is well established, the balance between these inputs is tipped toward immunosuppression. We found that a Toll-like receptor 9 (TLR9) ligand, CpG, induces the expression of OX40, an alternate costimulatory receptor, on CD4 T cells when it is injected into the tumor microenvironment. This is an indirect induction, in which CpG induces cytokine secretion by myeloid cells which in turn induces OX40 expression on T cells. Then OX40 can be activated using anti-OX40 antibodies, thereby activating TH cells in the tumor.

A. What is CTLA4 and how does it establish immunosuppression?

B. What is a costimulatory receptor, and why is an alternate one required here?

C. How does a TLR ligand such as CpG induce cytokine expression by myeloid cells? What myeloid cells are involved here?

D. How do antibodies that recognize OX40 help to stimulate TH cells? (Hint: think about autoimmune diseases. There is one we didn’t talk about, called Graves’ disease, that you might want to look up, too.) What else is required for the TH cells to become activated? E. How does all of this kill the cancer cells? What other cells in the tumor also must become activated? How? F. How does this differ from the CAR-T cell therapy?

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