NAME (PRINT)____________________________________________SID ___________________

PAGES WILL BE SEPARATED FOR GRADING. PRINT YOUR NAME AND SID
CLEARLY ON ALL PAGES OF THE EXAM, INCLUDING THIS COVER SHEET.

The exam contains 9 questions for a total of 120 points and you will be allowed 80
minutes. The point values of the questions are indicated in the table below and on each
sheet.

Make sure your exam has all 11 pages (this cover page plus 10 pages of questions).

Short succinct answers are sufficient, and the space provided should be adequate. In the
unlikely event that you need additional space, please consult your GSIs to get
permission before writing on the back of the same page. Do not write on the opposite
page, because the pages will be separated for grading.

Answer questions in ink, not pencil. Answers written in pencil will not be considered
for regrading.

Question Point Points

value
1 16
2 15
3 10
4 8
5 17
6 9
7 12
8 17
9 16
TOTAL 120

MCB132 – F13 – Midterm 1 1 10/1/13

NAME (PRINT)____________________________________________SID ___________________

1. (16 points) Mutiple choices: select all that apply.

a. Which of the following schematics MOST likely describes the correct order of cellular changes that
occur in the progression of malignancy?
A. Normal → hyperplastic → dysplastic → neoplastic → metastatic
B. Normal → dysplastic → hyperplastic → neoplastic → metastatic
C. Normal → hyperplastic → dysplastic → metastatic → neoplastic
D. Normal → neoplastic → dysplastic → hyperplastic → metastatic
E. None of the above

b. Malignant tumors
A. Always contain a single cell type.
B. Have acquired characteristics of invasiveness.
C. Are surrounded by an intact basement membrane.
D. Are often described as being in-situ.
E. C and D.

c. Dulbecco and Rubin discovered that they could infect chicken embryo fibroblasts with RSV in
culture. Which of the following was NOT a characteristic exhibited by these cells after they were
infected?
A. Virus particles were produced by these cells for many weeks.
B. Cells formed clusters, or foci, after infection.
C. The cells seemed to demonstrate uninhibited proliferation.
D. The cells exhibited flattened morphology.
E. The cells exhibited metabolic properties similar to those observed in tumor cells.

d. Which of the following is a property of transformed cells?

A. Rounded shape
B. Reduced requirement for mitogenic growth factors
C. Loss of contact inhibition
D. Increased transport of glucose
E. All of the above

MCB132 – F13 – Midterm 1 2 10/1/13

NAME (PRINT)____________________________________________SID ___________________

e. Once a cell has been infected with a virus, how might viral genes be transmitted from mother to
daughter cells?
A. Viral DNA carries its own replication machinery, replicating its own genome independently of
host enzymes.
B. Viral DNA may be integrated into the host cell’s chromosomes, so that it is replicated along
with host DNA prior to cell division.
C. Viral DNA replication may require viral encoded proteins in addition to host DNA replication
enzymes.
D. B and C.
E. All of the above.

f. Which of the following is true of retroviruses?

A. They are DNA viruses.
B. Their replication cycle requires DNA to be transcribed to RNA.
C. The DNA versions of their viral genomes are called proviruses.
D. B and C.
E. None of the above.

g. Scientists may map the insertion sites of viruses in DNA isolated from tumors that formed following
retroviral infection in order to
A. Identify the viral genes responsible for transformation.
B. Discover new proto-oncogenes.
C. Determine how viruses suppress tumorigenesis.
D. Understand how viruses infect cells.
E. All of the above.

h. DNA from human lung tumor cells was used to transfect NIH 3T3 (mouse embryo fibroblast) cells.
After several weeks, some of these cells formed foci, or clusters of cells, on the plate. Cells isolated
from these foci were able to grow in soft agar and formed tumors when injected subcutaneously into
immunocompromised mice. These results suggest that
A. The oncogene present in the human lung tumor cells is also able to transform NIH 3T3 mouse cells.
B. The NIH 3T3 cells were most likely transformed by multiple oncogenes present in the donor cells.
C. The NIH 3T3 cells were most likely transformed by a single oncogene present in the donor cells.
D. A and C.
E. A, B, and C.

MCB132 – F13 – Midterm 1 3 10/1/13

NAME (PRINT)____________________________________________SID ___________________

2. ( 15 points) Please determine whether the following statements are true or false. If false, please
explain briefly why in 1-2 sentences.
a. Retrovirus-associated oncogenes are often related to the oncogenes found in increased copy numbers
in non-virally induced tumor cells.

b. Following serum starvation, if normal fibroblasts were treated with cycloheximide to shut down
cellular protein synthesis, then, when exposed to fresh serum, the cells would continue to remain viable
in a quiescent state.

c. β-catenin binds directly to the Wnt protein in the cytosol and upon activation, translocate into the
nucleus where it associates with Tcf/Lef transcription factors to drive cell proliferation.

d. The ability of cells suspended in soft (semi-solid) agar medium to form colonies is a good predictor
that these cells will form tumors if injected subcutaneously into mice.

e. Analysis of a patient’s lung tumor reveals that all of the malignant cells in this tumor have a specific
chromosomal abnormality involving a fusion event between two sets of chromosomes. This MOST
likely suggests that this mutation was inherited.

MCB132 – F13 – Midterm 1 4 10/1/13

NAME (PRINT)____________________________________________SID ___________________

3. 10 points
a (2 points).What is the difference between an adenoma and an adenocarcinoma?

b (2 points). What is the difference between a carcinoma and a sarcoma?

c (2 points). In humans, which is more common, carcinoma or sarcoma?

d (4 points). What is the difference between invasion and metastasis?

4. 8 points

a. (6 points) Draw a fully-labeled diagram of the provirus of an avian leukosis virus, showing the
structure of regulatory elements and protein-coding genes.

b. (2 points). What is the experimental evidence that continued expression of the v-src gene is required
to maintain the transformed state of Rous sarcoma virus infected cells?

MCB132 – F13 – Midterm 1 5 10/1/13

NAME (PRINT)____________________________________________SID ___________________

5. (17 points)
a. (8 points). Genetic inactivation of an autoinhibitory mechanism is a common way in which the
products of proto-oncogenes can be activated in cancer. Explain how this occurs in the following
instances; your answer should include a description of the nature of the genetic change in the proto-
oncogene and the functional change in the protein product.
i. ras activation in pancreatic cancer

ii. abl activation in chronic myelogenous leukemia

iii. kit activation in familial (hereditary) gastrointestinal stromal cancer

iv. raf activation in melanomas

b. (3 points) Would you expect a drug that inhibits MEK to inhibit transformation by a murine sarcoma
virus carrying the v-raf oncogene? Why or why not?

MCB132 – F13 – Midterm 1 6 10/1/13

NAME (PRINT)____________________________________________SID ___________________

c. (3 points). Would you expect a drug that inhibits the EGF-receptor to inhibit proliferation of cancer
cells with a mutant PI-3-kinase (constitutively active)? Why or why not?

d. (3 points) What is the drug herceptin and why is it more effective on some breast cancer patients than
others?

6. (9 points).

Protein-protein interactions may be mediated by specialized protein modules or domains. For each of the
following domains, state what structure the domain recognizes, then give an example of a protein
containing the domain and explain the importance of the domain in the function of the protein.

i SH2 domain

ii. SH3 domain

iii. PH domain

MCB132 – F13 – Midterm 1 7 10/1/13

NAME (PRINT)____________________________________________SID ___________________

7. 12 points

a (3 points). Cells transformed by simian sarcoma virus proliferate in low serum medium. This
proliferation is inhibited by antibodies against PDGF. Why?

b. (3 points). What is the cellular progenitor of the v-erbB gene of avian erythroblastosis virus, and how
do the protein products of the viral and cellular genes differ in structure and activity?

c. (3 points). Point mutations are found in the juxtamembrane segment of Kit in gastrointestinal stromal
cancer. Why do these mutations activate Kit?

d (3 points). In certain cancers, genes encoding receptor tyrosine kinases undergo translocations and
now encode fusion proteins. Why are the kinases activated?

MCB132 – F13 – Midterm 1 8 10/1/13

NAME (PRINT)____________________________________________SID ___________________

8. 17 points
a. (4 points) The expression of a certain proto-oncogene is invariably associated with Burkitt’s
lymphoma. What is this proto-oncogene (2 point), and how is its expression increased in Burkitt’s
lymphoma (2 points)?

b. (13 points) Below is shown a comparison of tumor cell DNA with normal DNA, showing the relative
abundance of different segments of the genome.

i. How are such data obtained? (5 points). Your answer should include the name of the technique and a
very brief description.

ii. What is shown on the abscissa (x-axis)? (2 point)

iii. What is shown on the ordinate (y-axis)? (2 point). (Note: the ordinate is plotted on a logarithmic
scale, you do not need to explain this).

iv. What conclusion can be drawn from these data? (4 points)

MCB132 – F13 – Midterm 1 9 10/1/13

NAME (PRINT)____________________________________________SID ___________________

9 (16 points)

a) (6 points) One familiar cancer syndrome we learned about in the first section of the course is familial
adenomatous polyposis, or adenomatous polyposis coli. What protein is mutant in this disorder, what is
its biochemical function, and how does it affect Wnt signaling?

b) (5 points) Activating mutations in one of the components of the Wnt pathway occur in prostate and
colon cancers, although not at a high frequency. What is this protein and what is its biochemical
function?

c) (5 points) Inactivating mutations in the protein you described in part (a) and (more rarely) activating
mutations in the protein you described in part (b) both occur in sporadic colon cancer. How do these
mutations lead to polyp formation? Your answer should focus on the role of Wnt signaling in cell
proliferation in the normal intestinal epithelium and how alterations in Wnt signaling affect the
regulation of cell proliferation. A detailed description of the biochemistry of the Wnt pathway (over and
above what you have included in parts (a) and (b)) is NOT required.

MCB132 – F13 – Midterm 1 10 10/1/13