Cancer Genetics Flashcards
How may cells are in the Human body?
There are 37 trillion cells in the human body. There are many types of tissues.
(body has to have continuous division of cells to generate these cells)
What are the different types of cells?
Types of cells:
-nerve cell (transmit info within body)
Muscle cells (thick cells full of myosin fibers that contract to move the body)
bone cells
Gland cells
Blood cells (RBCs can carry Hemoglobin and be smooth)
Reproductive cells (sperm tiny and carry DNA; egg must be huge and carry DNA)
(wide variety of cells that are controlled by gene that regulate development)
What is the life span of the different kinds of cells (brain, liver, RBC, skin cells and stomach lining cells) ?
Some cells have very short life spans
Brain cells = 30-50 years
Liver cells= 200 days
Red blood cells= 120 days
Skin cells= 20 days
Stomach lining cells= 2 days
(body tends to generate new cells to replace the old ones)
(We must control the pattern of cell division through our lives and also control how cells develop )
What is the goal of chemoterha
Chemotherapy- it is trying to kill bad cells; This chemotherapy process kills all cells that are dividing
-Hence why people lose hair, and feel very sick, weak.
What are the three key process that cells undergo? What signals do cells have?
All cells face three key processes (choices) :
-Differentiation
-Growth and cell division
-Cell death (Apoptosis)
Signals:
-growth factors
-steroid hormones
-cell-cell interactions
What causes cancer?
Differentiate between benign and malignant tumors
Cancer is caused by the UNCONTROLLED division of cells
-these cells have become ABNORMAL through genetic changes
-Tumors can be Benign- large growths that are restricted to one location and usually NOT harmful
-Tumors can be Malignant or Cancerous by gaining the ability to invade other tissues and spread in the body.
(these cells keep dividing and migrating through body)
Desciteb the The”Two Hit Theory of Cancer” and the meaning behind it. Who discovered this theory? Why is it significant?
The two-hit theory of cancer : describes how TWO MUTATIONS are needed to cause cancers
-one mutation is not usually sufficient to cause cancer
Two Hit Theory (Alfred Knudson) described how mutations act together to initiate a cancer
-Eventually many mutations play a role in tumor formation, growth and metastasis
What are Retinoblastomas ?
Retinoblastomas are RARE cancers of the retina
(images show tumors growing in both left and right eye of a patient with retinoblastoma)
How are Retinoblastomas inherited?
Some retinoblastomas are inherited
-Mutations in the RB gene cause retinoblastomas
-These mutations are DOMINANT
-The Rb mutations inactivate the gene
-Thus Rb mutations are Haploinsufficient for cancer risk
What happens when there is a Rb allele? how does this affect risk of cancer? What factors did Knudsen consider in regards to retinal cells?
An Rb allele creates a risk that a mutation in the good Rb gene will cause cancer
Knutson considered:
-The number of susceptible retinal cells
-The number of tumors found in each eye
-Age of onset
Based on this, he calculated a mutation rate of:
u= 2 x 10^-7 per cell per year
-The rate for spontaneous retinoblastomas is similar
Describe the types of cancers seen in patients base on frequency in Rb/+ (heterozygous genotype)
Type of Cancer——-> Frequency in Rb/+
Unaffected ————> 1-10%
Unilateral (1 eye) ——-> 25-40%
Bilateral (2 eyes) ——-> 60-75%
eye function and tumors in people who were heterozygous for mutation (small number were unaffected; largest group at mutation in both eyes)
- if you are heterozygous for mutation, one copy of gene is already NOT working (you only need second copy of gene to be affected for cell to be tumor )
-individuals who start without no mutations in retinalblastoma have a LOWER chance of getting disease, because they would first need one mutation in one copy of gene and descendant of cell will have to get other mutated copy (Rare case of getting disease)
What can cause you to get high chance of developing cancer?
if the gene protects you from cancer and you already missing one good copy of gene; the other gene is now at risk .If any of the the trillion cells gets a mutation in surviving good copy, get high chance of developing cancer.
What is the Poisson Distribution? How does it work?
Poisson Distribution: calculation used to predict distributions
-We can use it if an event:
-can be repeated
-Each case is independent
-Occurs at a regular frequency
-Let the average number of events = lambda
Then the chance of Zero events - e^lambda
In general, the chance of k events = lambda^ke- lambda/k! (factorial )
k=1 or 2 or more events
factorial (ex: 5! is 5x4x3x2x1)
Provide an example of when you can use the Poisson distribution
Example: Woburn Leukemia cluster
-in Early 1990s, a leukemia cluster (of 8 cases) was identified in Massachussetts town of Woburn. Many more cases of leukemia, a malignant cancer that originates in a cel in the marrow of bone, appeared in this small town than would be predicted.
Goal: Determine the probability of this cluster, was due to chance, NOT carcinogens
-
How would you set up the Poisson distribution for example of Woburn Leukemia center?
Setting up Poisson distribution
Key initial information you must find out:
-chance of getting leukemia f= 0.00011
Population of Woburn = 35,000
First thing to calculate
-Expected number of cases = lambda= 35000 x 0.00011= 3.85
(figuring out chance of getting 8 or more cases; include rare cases)
Then Applying the Poisson Distribution union
P(0)= e^-3.85= 0.0213
P(1) = (3.85)^1 x e^-3.85/1!= 0.0819
P(2)= (3.85)^2 x e^=3.85/2!= 0.1577
P(3) = (3.85)^3 x e^3.85/3!= 0.2024
P(4)=(3.85)^4 x e^-3.85/4!= 0.1948
P(5)= (3.85)^5 x e^-3.85/5!= 0.1500
P(6)= (3.85)^6 x e^-3.85/6!= 0.0962
P(7)=(3.85)^7 x e^-3.85/7!= 0.0529
Total chance for 1-7 cases (add values up) = 0.9572
-so 95.72% of towns of 35000 should have only 7 or fewer cases of leukemia
-There was a chance of 4.28% that the Woburn cluster was due purely to chance
-Based on these odds, local chemical companies settled with families on the presumption that the trichlorethylene wast in local drinking water causes these cancers.
Where do Cancers result from?
Cancers result form the Accumulation of mutations in a cell line
(a cell will divide and then daughters will divide;
process of cells constantly dividing and one gets a mutation and one of its second descendants get another mutation, and then another mutation that leads to cancer)
-build up of mutations between descendants lead to uncorontrollable growth in the cell (Cancer)
ex; Colon Cancer
Explain what happens in Colon Cancer
Colon cancer : that occurs due to one mutation in tumor suppressor gene (APC) that changes cell and causes small benign growth. Then second mutation that activates another gene (ex; Ras Oncogenes) and third tumor affecting another gene, you get Larger benign growth and get additional mutations that allow cell to move causes malignant cell which spreads through body and can kill
-hence early detection of cell growth before mutations accumulate.
What kind of mutation can start the process of cancerogenesis?
A new somatic mutation might start the process of cancerogenesis
-a first mutation and second mutation can occur and lead to early tumor formation
(mutation happening in cell and in its descendant cell leading to lethal combination)
Which mutation is higher than the gremline rate?
The SOMATIC mutation is HIGHER than the germ lie rate
We have good control on mutation rate in our germ cells (cells that make eggs or sperm)
-the cells that make up our body have higher mutation rate (fewer protection) the risk of mutations that may cause cancers are higher.
The body accumulates somatic chromosomes on EVERY chromosome
What correlates with the mutation frequency?
The RISK of CANCER correlated with the mutation frequency in particular cells
(cells with low mutation rate, low cancer risk;
cells with higher mutation rate, higher cancer rate)
What can also help start a cancer?
DELETIONS of part of a chromosome can also help start cancer
(ex: the loss of an entire arm or half an arm of chromosome can be severe)
mutations in individual genes (ex: point mutations) cause gene to change function and promote tumors)
What can start the process of cancergenesis?
An INHERITED mutation might start the process of cancerogenesis and make it much more likely to proceed
(if one carrying Rb1 mutation passes it on to child; child already starts Rb1 (retinoblastoma) mutation and only need one more mutated copy to get cancerous cell.
Descirbe the different types of cancer genes? How do they affect cells.
Types of cancer genes
some mutation affect ONCOGENES: (Onco–> cancer)
-Proto-oncogens: are normal genes
-Oncogenes are Mutant genes that cause cancer (cell divides abnormally)
Some mutations affect TUMOR SUPPRESSORs:
-The body has elaborate mechanisms to protect it from cancer
(tumor suppressor genes carry out protective role of recognizing and preventing cancers from forming in the body)
-These methods depend on tumor suppressor genes like Rb
-Mutations in these genes weaken the bodies defenses.
(prevent body from defending itself)
How were oncogenes discovered? What are Viral oncogenes? Provide examples. How do they affect cells?
Oncogenes were first discovered with people studying Viral oncogenes
Viral Oncogenes: some viruses can induce cancers
-Epstein-Barr Virus
-Hepatitis B and C
-Human papillomavirus
-Some viruses cause mutations by integrating into human DNA at random locations
-Some viruses make proteins that cause cancer by affecting the cell cycle
