Module 13: Cancer

What is metastasis?

it occurs when malignant cancer cells enter the blood stream (or lymphatics) and spread to other locations in the body.

What causes cancer?

Cancer is caused by the accumulation of mutations that promote uncontrolled cell proliferation.

Do cancer promoting mutations usually cause gain of function or loss of function?

Cancer promoting mutations in tumor suppressor genes are usually loss of function, recessive mutations.

What is a tumor suppressor gene?

A tumor suppressor gene is a gene whose *loss of activity* contributes to uncontrolled cell proliferation.

What is a carcinogen?

An agent that promotes cancer.

Why is an inherited predisposition to developing a cancer usually due to inheriting a mutation in a tumor suppressor gene rather than in an oncogene?

An individual usually inherits a mutation in one copy of a tumor suppressor gene, which does not affect development. A mutation is acquired in the second copy later in life. If an individual inherited a mutation in an oncogene then it would probably be fatal during development or it would promote the very early development of a cancer, so the mutation is less likely to be transmitted over generations.

How do oncogenes contribute to uncontrolled cell proliferation?

Oncogenes encode proteins that *promote cell division or prevent apoptosis.* If a protein promotes cell division, then its over-activity may produce uncontrolled cell division. If a protein normally prevents apoptosis, then its over activity may inappropriately prevent mutated cells undergoing apoptosis, so the mutated cells will continue to survive and proliferate.

Consider the following mutations, and, for each, explain whether you expect it to be a) potentially cancer promoting) dominant or recessive iii) A point mutation that renders one of the signaling proteins in the cell division pathway constitutively active

The mutation would probably be dominant because it is gain-of-function, and the mutation WOULD be cancer promoting because it promotes cell proliferation.

Consider the following mutations, and, for each, explain whether you expect it to be a) potentially cancer promotingb) dominant or recessive i) A mutation that destroys the active site of an enzyme necessary to promote cell cycle progression

The mutation would probably be recessive because it is loss of function. The mutation WOULD NOT be cancer promoting because it does not promote cell proliferation.

Consider the following mutations, and, for each, explain whether you expect it to be a) potentially cancer promoting) dominant or recessive iv) A null mutation in a gene encoding an apoptosis-promoting protein

The mutation would probably be recessive because it is loss of function. The mutation WOULD be cancer promoting as it would allow cell proliferation in a cell that would normally undergo apoptosis.

Consider the following mutations, and, for each, explain whether you expect it to be a) potentially cancer promoting) dominant or recessive ii) A very premature STOP codon in a gene encoding a protein involved in DNA repair

The mutation would probably be recessive because it is loss of function. The mutation WOULD be cancer promoting because any future cancer-promoting mutations may go unrepaired.

How do tumor suppressor genes contribute to uncontrolled cell proliferation?

Tumor suppressor genes encode proteins that *prevent cell division, promote apoptosis or promote DNA repair.* If a protein prevents cell division, then its loss of activity will enable cells to proliferate. If a protein usually promotes apoptosis, then its loss of activity means that mutated cells may not be programmed to die and mutated cells will continue to survive and proliferate. If a protein usually repairs DNA, then its loss of activity means that cancer promoting mutations will not be repaired.

What is an oncogene?

a gene that, when *over-active,* contributes to uncontrolled cell proliferation.

What is a malignant tumor?

an overgrowth of abnormal cells that are no longer under normal cellular regulation and have the ability to proliferate out of control and invade other tissues.

What is a benign tumor?

an overgrowth of normal cells. In a benign tumor, the cells are still under normal cellular regulation and cannot invade other tissues in the body. If the cells acquire more mutations over time, the benign tumor can turn malignant.

Do cancer promoting mutations in oncogenes usually cause gain of function or loss of function?

they are usually gain of function dominant mutations.