Application C - Cancer
There are two types of Lynch syndrome, what are they?
1. Lynch syndrome II (noncolonic cancer of stomach endomentrium, biliary and pancreatic systems) 2. Lynch syndrome I (hereditary nonpolyposis colorectal cancer)
Choose the normal functions of the protein products of these genes. MSH1 + MSH2
1. MSH1 codes for a protein that is part of a complex of proteins that repairs the DNA in the region identified by MSH2 2. MSH2 codes for a protein that identifies regions of DNA that contain mistakes in DNA replication by binding to DNA that contains mismatched base pairs.
How are cancer cells different form normal cells?
1. cancer cells are dedifferentiated = looks and behaves like primordial cells 2. higher rate of proliferation 3. larger and has a larger nuclei than normal cells 4. exhibits poor organization as they grow, while normal cells are very organized and confined to boundries
what are the stages of cancer progression?
1. hyperplasia 2. dysplasia 3. neoplasia 4. metastasis
What are the ten hallmarks of cancer?
1. sustained cell proliferation 2. evasion of normal growth suppression 3. resistance to cell death 4. cellular immortality 5. angiogenesis induction 6. activation of invasion and metastasis 7. reprogramming of energy metabolism 8. immune system avoidance 9. tumor-promoting inflammation 10. genome instability and mutation
What percentage has cancer deaths decreased by due to advancement of cancer screening, research, and treatment?
20%
What percentage of cancer cases are thought to be associated with inherited mutations that predispose individuals to cancer? 1. 50-55% 2. 90-95% 3. 20-25% 5. 5-10%
5-10%
What is the cause of CML?
A shorter translocated chromosome called Philadelphia chromosome that contains c-ABL-BCR/fusion gene that leads to continuous stimulation of cell division
What are the 4 genes that are often mutated as polyps progress towards malignancy
APC, KRAS, DCC and TP53
BRCA1 and BRCA2 Onsets
BRCA1 - onset is 70 w/ 60% breast cancer and 59% ovarian cancer BRCA2 - onset 70 with 55% breast cancer and 16% ovarian cancer
After pRB binds to E2F, what happens next?
Cyclin D1-CDK4 phosphorylates pRB near the end of G1 before S-phase begins, which causes the release of E2F, and it moves to the nuclues where it activates transcription of genes needed for s-phase
The activity of which of the following proteins is directly regulated by the pRB protein product of the RB1 gene?
E2F
Epigenetic Irregularities in Cancer
Epigenetic proccesses that can disrupt cancer 1.epigenetic regulation can be abnormal 2. mutation of epigenetic readers, writers, and erasers can alter epigenetic patterns in cells
What are the approximate rates of cancer that develop in people carrying a mutation of one of these genes? MSH2
For mutations in MSH2, the lifetime risk of developing some type of cancer was 91% for males and 69% females.
What genes are most commonly mutated in Lynch syndrome?
MSH2 gene and MLH1 gene
Can you say with certainty that a woman inheriting a mutation of BRCA1 will definitely develop breast cancer in her lifetime? Why or why not?
One cannot conclude with certainty that a woman with a BRCA1 mutation will get breast cancer. Only 60% of women with certain BRCA1 mutations are expected to develop breast cancer by age 70.
What are other DNA methylation genes other than DNMT3A
TET2 and IDH
What gene discussed in this chapter might be responsible for pausing the cell cycle of dividing cells long enough for radiation-induced damage to be repaired in cells?
TP53 gene
TCGA
The Cancer Genome Atlas; a compile of genome sequence and analysis of somatic genetic mutations of thousands of tumors of different types
In their normal state, what is the primary function of the protein products of the BRCA1 and BRCA2 genes?
They detect and repair DNA damage.
Separate as tumor suppressor genes and proto-oncogenes: TP53, RB1, APC, and c-MYC
Tumor Suppressor Genes: TP53, RB1 and APC Proto-oncogenes: c-MYC
Can a tumor arise from a single mutated cell? Are all the cells in a tumor identical?
Yes, a tumor can arise from a single, mutated cell, and it typically contains cells that are genetically heterogeneous
Do you think it is possible that significant increases in the incidence of other types of cancer will occur in the future among people who were exposed to the Fukushima radiation? Why?
Yes, it is possible, because radiation causes DNA damages in most/all cell types.
Where is the mutation in Burkitt's Lymphoma?
a de novo reciprocal translocation between chromosome 8 and chromosome 2, 14, or 22
What are tyrosine kinase inhibitors (TKIs)?
a drug that target the BCR-ABL tyrosine kinase enzyme and is a medication for people with CML. it causes the BCR-ABL enzyme to stop working which causes the CML cell to die
What kind of disease is cancer?
a genetic disease that results from multiple gene mutations in somatic cells of the body
Familial adenomatous polyposis (FAP)
a genetic predisposition to cancer, specifically 1-2% of colorectal cancer
what are tumors?
a mixture of malignant and normal cells
What mutation causes LFS
a mutation of the TP53 gene (tumor protein 53/AKA p53) that encodes transcriptional factor that regulates expression of 50+ other genes
What is Sporadic Retinoblastoma
a rare retinal cancer that occurs in newborn infants and very young children. Where eye development occurs and stops after a few months
Where is the mutation in Chronic Myelogenous Leukemia (CML)?
a reciprocal translocation between chromosome 9 and chromosome 22
How does retinoblastoma come about?
a second mutation occurs that affects the wild-type copy of RB1 in any somatic cell of a developing retina
Why is E2F important?
activates that trascription of S-phase genes, and when bound by pRB it is prevented from acting as a TF
what is the greatest risk of cancer?
age
What is Li-Fraumeni Syndrome(LFS)?
an autosomal dominant that is inherited, involves different organs and tissues with cancer cases
What happens in Burkitt's Lymphoma?
an overexpression of the c-MYC protein which drives excessive cell division
What happens in CML?
an overproduction of white blood cells called granulocytes
TP53 (p53)
blocks cell cycle to allow time for repair of DNA damage; if the pause is too long, TP53 initiates apoptosis
What is the cause of Sporadic Retinoblastoma?
both copies of the RB1 gene are mutated on chromosome 13, removing the pRB protein and occurs with a single tumor in only one eye
BRCA1 and BRCA2
breast cancer 1 and 2 - genetic mutations associated with increased risk for breast cancer DNA damage repair genes, can reduce/eliminate the ability of the protein to function normally
Before the cells become cancerous, how do the cells appear?
can appear as hyperplasia (extra growth) and can lead to dysplasia (disorganized growth), from dysplasia it can lead to neoplasia (fast and disorganized growth) and finally to metastasis (invading and traveling to new locations to form new tumors)
What is the most common cause of death?
cancer
Which of the following characteristics is NOT one of the four general ways in which cancer cells differ from normal cells? 1. Cancer cells are larger and also have larger nuclei 2. cancer cells have a high rate of proliferation 3. cancer cells are dedifferentiated 4. cancer cells are highly organized
cancer cells are highly organized
What happens if there is a mutation in the DNMT3A
causes hypomethylation, where if there it's not mutated it would help methylate chromatin for gene silencing
what are benign tumors?
cells that remain clustered together and usually these tumors are harmless
Targeted cancer therapy
find specific aspect of a tumor and use it as a target for treatment
what happens if the tumor-suppressor gene is mutated?
if mutated it allows the cell cycle to proceed when it should pause or stop at a checkpoint
How do each cancer disease differ?
in growth rate, degree of invasiveness, age of onset, responsiveness to treatment, and prognosis
When does hereditary retinoblastoma occur?
is an early onset in both eyes
when visually looking at an cancer genome, what does it look like?
large number of duplications, deletions, chromosome rearrangements, and changes in chromosome number
Breast and Ovarian Cancer Inherited
less than 10% of cases, generally bilateral cancer, onset is 30-40s. Inheritance pattern is similar to autosomal dominant
What happens in LFS
main cause is by CHEK2 mutation (checkpoint kinase 2) continuous production of TP53 that is also being continuously destroyed, stress to cells and high levels of DNA damage
The term ________ refers to cells that are not confined in their growth and invade normal tissues? 1. dysplasia 2. metastasis 3. neoplasia 4. hyperplasia
metastasis
what are oncogenes?
mutated forms of overstimulated cell division
In addition to inheriting a BRCA1 mutation, what else must happen for a woman to develop breast or ovarian cancer?
mutations in tumor suppressor genes, mutations in proto-oncogenes and environmental factors
Which stages of the cancer progression are malignant?
neoplasia and metastasis
Breast and Ovarian Cancer
non inherited, 90-95% of this cancer are sporadic. avg age of onset is 60s. can occur in only one breast/ovary (unilateral)
what are tumor-suppressor genes?
normal genes that function largely at cell cycle checkpoints
what are proto-oncogenes?
normal genes that stimulate cell division and progress through the cell cycle
why is pRB important?
plays an essential role of controlling cell division and forms a complex with a transcription factor E2F. It is also a tumor suppressor
What type of chromosomal rearrangement generates the c-ABL-BCR "fusion gene"?
reciprocal translocation
What happens in Sporadic Retinoblastoma
retinal cells lacking the pRB protein that have an active transcription factor protein (E2F) that drives excess retinal cell division
Which of the following functions is NOT associated with the TP53 protein? 1. initiating apoptosis 2. pausing cell cycle 3. stimulating DNA damage repair 4. stimulating angiogenesis
stimulating angiogenesis
What is the cause of Burkitt's Lymphoma
the c-MYC gene on chromosome 8 is moved from a region where it is regulated to a region on the recipient chromosome where it is continuously expressed
how do epigenetic changes affect cancer cells?
the cancer cell's metabolism and cancer immunology
