Download MCDB 1041 Class 36: Genetics of Cancer

MCDB 1041
Class 36: Genetics of Cancer
Learning goals
•  Describe how cells become cancerous, and how cancer spreads
•  Explain how the kinds of mutations that usually lead to
cancer affect the cell
•  Relate onset of cancer to the genes involved in the
progression of the cell cycle
•  Explain where the cell cycle has checkpoints and what these
checkpoints are testing for.
•  Predict the effects of losing one of the checkpoints.
•  Cancer is a group of diseases characterized by
out of control cell division and ability to spread
throughout the body
•  Cancer is caused by mutations in DNA, but is
not necessarily inherited
Why Do We Care About Cancer?
–  2nd Leading cause of death in the US, behind
heart disease
•  Around 500,000 Americans are expected to die this
year from cancer
–  The total economic impact of cancer in the US
is estimated to be 228 billion dollars
http://www.pbs.org/pov/inthefamily/
video_classroom3.php#.UVscVhnagZ0
Cancer is a genetic disease
•  Cancer arises from the accumulation of genetic
changes (mutations)
•  Most cancers have a minimum of 6-9 different genes
mutated
•  We do not directly inherit cancer: we can only pass on
susceptibility to cancer.
•  Many genes that are mutated in cancer code for
proteins that are involved in regulating the cell cycle
Cancer: Unregulated Cell Division
Cell Division: One part of the cell cycle
Cell Cycle: How cells normally
reproduce to replace cells
Cancer
•  Mis-regulating the cell cycle.
–  Cells divide when they aren’t supposed to.
–  Cells divide in a place they aren’t supposed to.
•  How does the cell normally coordinate this process?
Handout
Cell Cycle Overview
On your sheet of paper, use these terms below to mark
the arrows and make simple pictures of the cell at
different stages to create your own cell cycle diagram.
Chemotherapy Agents
Indicate on your diagram where the three major types
of chemotherapy agents would work:
Inhibitors of DNA Duplication
Inhibitors of Cell Division
Inhibitors of Cell Growth
What would happen if the cell cycle proceeded normally, except that cell division did not occur? A.  The cell growth phases would become shorter. B.  The separa6on of chromosomes couldn’t occur. C.  The resul6ng cells would get smaller and smaller. D.  Cells without nuclei would be formed. E.  A large cell with mul6ple nuclei would result. There are three major points where the cell checks the
progress of the cell cycle to insure that all is ready to
proceed to the next step. Place these three “Checkpoints”
on your diagram:
Checkpoints
1 Cell Size Big Enough?
1.
DNA undamaged before copying?
2. All Chromosomes Attached
2
to spindle and aligned?
3.
3 All Genetic Material Duplicated? Environment Favorable?
Indicate the location of each cell cycle checkpoint
III I 1.  Cell Size Big Enough? DNA
undamaged before copying?
2.  All Chromosomes attached to
spindle and aligned?
3.  All Genetic Material Duplicated
and undamaged? Environment
Favorable?
A. 
B. 
C. 
D. 
II= 3; III=2; IV= 1
II= 1; III= 2; IV=3
I= 1; II=3; IV= 2
II= 1; III=3, IV=2
DNA damage such as double strand breaks are detected at
G1/S checkpoint by a protein called ATM. ATM activates
another protein called p53 that halts the cell cycle at
that checkpoint. If you were testing a new drug designed
to activate the p53 protein, you could look for cells that
were successfully arrested at this G1/S checkpoint by:
A.  determining if the amount of DNA is at half the level of
a normal cell.
B.  counting chromosomes, arrested cells would be missing
some.
C.  determining if the amount of DNA per cell always
remains the same rather than doubling during S phase.
D.  determining if a spindle forms but never gets broken
apart.
What genes typically get mutated to
lead to cancer?
Types of cancer-causing genes
Type of gene
Normal function
Tumor
suppressor
Suppresses cell
division
ProtoOncogene
Promotes division Promotes division
Repair genes
Mutated function
Fails to suppress
division
at abnormal
levels, or in
cells that
shouldn’t divide
Repair DNA
mutations
Fail to repair
DNA
mutations
Types of proteins
Growth factor
inhibitors
Growth factors
Enzymes
If you lose the function of a tumor suppressor gene,
what do you think would happen?
a.  Decreased cell division
b.  Increased cell division
c.  No cell division
Tumor suppressors normally put a
stop to division: they make cells
go into G0 rather than continuing
into S phase
Mutations in tumor suppressor are recessive
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Homozygous&&&&&&&&
wild&type&(+/+)&
Normal&cell&division&
Heterozygous&(+/>)&
*&&
Normal&cell&division&
Homozygous&&
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*&& *&&
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Proto-oncogenes act dominantly at the cellular level
•  Genes that promote cell
division when mutated,
become “oncogenes”
•  Cancerous situations:
•  Expression of oncogene at
the wrong time or in the
wrong cell type
•  Mutation (dominant)
causes protein to always
“ON”
What causes mutations?
Most mutations are random, caused by “carcinogens”:
Radiation
UV light
Some foods
Chemicals
In addition, a mutation can be inherited from a
parent, resulting in a higher chance (predisposition)
of getting cancer (as in the BRCA1 scenario).