Lecture 2: Oncogenes

Question 1

German pathologist who originally proposed the concepts of genes that suppress cell proliferation and genes that cause cell proliferation.

Answer 1

Theodor Boveri

Question 2

A variant of a normal gene that has acquired a gain-of-function alteration.

Answer 2

Oncogene

Question 3

A normal gene that can become an oncogene.

Answer 3

Proto-oncogene

Question 4

How can proto-oncogenes become oncogenes?

Answer 4

1) Point mutations
2) Chromosome rearrangements
3) Amplification of the proto-oncogene sequence

Question 5

What was the first oncogene discovered?

Answer 5

SRC

Question 6

What type of protein does SRC encode for?

Answer 6

src, a cytoplasmic kinase

Question 7

Who discovered RSV and how? What is the significance of this discovery in the history of cancer research?

Answer 7

Peyton Rous. He injected the liquid from mashed up chicken tumors into the leg of a healthy chicken, and this caused cancer in the healthy chicken. This demonstrated that tumors could be virally-induced in chickens.

Question 8

What does RSV stand for?

Answer 8

Rous Sarcoma Virus

Question 9

What enzyme in retroviruses allows the viral RNA to be reverse transcribed into DNA?

Answer 9

reverse transcriptase

Question 10

Which oncogene codes for the CSF-IR receptor? What type of receptor is CSF-IR?

Answer 10

fms; CSF-IR (colony-stimulating factor 1 receptor) is a growth factor receptor that controls the production and differentiation of macrophages

Question 11

What are macrophages?

Answer 11

White blood cells that engulf and digest cellular debris, foreign substances, microbes, cellular cancer, and anything else that does not have the types of proteins specific to a healthy body on its surface (phagocytosis).

Question 12

What oncogene affects the production of macrophages?

Answer 12

fms

Question 13

For what did Varmus and Bishop win the Nobel Prize?

Answer 13

For using a cancer-causing retrovirus (AVS) to identify the oncogenes in normal cells. They demonstrated that the the oncogene in the virus is not a true viral gene, but a normal cellular gene picked up by the virus during replication in the host cell and carried along thereafter.

Question 14

What types of cells have been mutated to produce a gain of function?

Answer 14

oncogenes

Question 15

How many mutations are needed to get a gain of function (oncogene)?

Answer 15

1

Question 16

What are genes that can be mutated to become oncogenes?

Answer 16

Proto-oncogenes

Question 17

What are three ways by which a proto-oncogene can become an oncogene?

Answer 17

1) Deletion or point mutation in the coding sequence (gives a hyperactive protein in normal amounts).
2) Gene amplification (normal protein is overexpressed–i.e., produced in large amounts)
3) Chromosome rearrangement (gene/protein fusions that result in overexpression or hyperactivity; or translocation of a gene to a nearby regulatory sequence, resulting in an overexpressed normal protein)

Question 18

What is the result of a deletion or point mutation that produces an oncogene?

Answer 18

This causes the protein to be hyperactive (even though it is still only present in normal amounts).

Question 19

What is the result of a gene amplification that produces an oncogene?

Answer 19

The protein will be normal, but will be over-produced (because mRNA activity is prolonged in the cell).

Question 20

What is the result of gene fusion chromosome rearrangement that produces an oncogene?

Answer 20

The transcription of the gene is regulated by regulatory sequences of another gene. This causes overexpression of the protein or a hyperactive fused protein.

Question 21

What is the result of the translocation of a gene to a nearby regulatory sequence (a type of chromosome rearrangement) to create an oncogene?

Answer 21

This causes the normal protein to be over-expressed.

Question 22

What five animals were used in Bishop and Varmus’ study of src?

Answer 22

Human, calf, mouse, chicken, and salmon