Lecture 21 Genetics Of Cancer

Question 1

Phenotypic changes in cancer cells
(Why does cancer have many different phenotypes?)
4 phenotypes and why

Answer 1

Cancer is a highly heterogeneous disease (many different forms)
Uncontrolled cell growth
Autocrine stimulation: cancer cells secrete growth factors that stimulate their own growth.
Loss of contact inhibition
Loss of apoptosis
Loss of gap junction: loss of cell to cell communication essential for growth regulation (contact inhibition, apoptosis) and cell organization.

Uncontrolled cell division

Increase the rate of mutation
Defects in DNA replication machinery
Cancer cells are unable to fix nucleotide mismatch, leading to accumulation of mutations.

Metastasis: Ability to disrupt local tissue and invade distant tissues
Cancer cells have angiogenesis ability to feed high metabolic and high proliferation rate.

Question 2

What give rise to cancer?
(2 aspects and 3 evidence each)

Answer 2

Induction of a tumor requires several mutations, each of which increases the cells chances of becoming malignant (multi-hit model of cancer development)
→ The complexity of human body processes.

Evidence
Incidence of cancer in humans increases with age
Later stages cancer have more mutations
Cancers are clonal descendants of one cell

Most cancer result from exposure to environmental mutagens
Evidence:
If one sibling in a twin gets cancer, the other usually does not.
incidence of developing specific type of cancer becomes more like that of people indigenous to new locations.
Exposure to known mutagens increases the risk of developing cancer.

known mutagen:
radiation
certain chemicals: cigarette
certain viruses

Question 3

Cancer genes
(What are cancer genes?)
Cancer genes type 1
____ of function, dominant/recessive mutation.
Genes involved in ____
(2 examples)
Function
Mechanism
Mutation causes ____

Cancer genes type 2
____ of function, dominant/recessive mutation.
Genes involved in ____
(2 examples)
Function
Mechanism
Mutation causes ____
Note for Rb

Answer 3

Mutated genes that are causally implicated in cancer development.

Proto-oncogenes
Gain of function, dominant
Genes involved in promoting cell growth and division/proliferation, inhibiting apoptosis.
RTK, ras: promoting cell division/proliferation
Receptor tyrosine kinase
cell proliferation is active when ligands are bound.
Mutation causes it to be continuously active, no longer ligand dependent.

Ras
cell proliferation is active when GDP is phosphorylated to GTP.
Mutation leads to no conversion of GTP to GDP, causing it to be continuously active.

Tumor-suppressor genes
Loss-of-function, recessive
Genes involved in inhibiting cell growth and division/proliferation, promoting apoptosis.

Rb: inhibits cell proliferation
Cell proliferation is inhibited when unphosphorylated Rb binds to E2F
Cell proliferation is active when Rb is phosphorylated by CDK cyclin and leaves E2F.

Mutation leads to Rb permanently phosphorylated, Causing cell division to be continuously active.

Note: Even though Rb mutation is recessive, people who are heterozygous can still develop cancer by induced mutation.

DNA repair genes

Question 4

The diagram below illustrates a cellular signaling cascade that occurs following the binding of a general growth factor necessary for cell proliferation. After repeated exposure to a mutagen you were able to generate a cell line with a loss-of-function mutation in the transcription factor gene, resulting in its inability to translocate to the nucleus to activate transcription. Which of the following would you expect as a direct or indirect consequence of this mutation
A) absence of contact inhibition
B) presence of programmed cell death
C) absence of gap junctions
D) presence of metastasis

Answer 4

B

Question 5

What is NOT an example of a phenotypic change associated with uncontrolled growth of cancer cells?
A) Division in the absence of external growth signals required for the proliferation of normal cells
B) Loss of contact inhibition
C) Gain of gap junctions to communicate with neighboring cells
D) Failure to enter apoptosis when damaged

Answer 5

C

Question 6

What is NOT true of the product of the retinoblastoma (Rb) gene?
A) The Rb gene product regulates the G1 to S phase transition in mitosis
B) The Rb gene product binds and inhibits the transcription factor E2F
C) Phosphorylating the Rb gene product prevents the cell from entering S phase
D) The Rb gene product is phosphorylated by CDK-cyclin complexes

Answer 6

C