quiz review ppt WY

Question 1

What is the function of RTK/Ras/NF1/MAPK?

Answer 1

Prosurvival path.

Question 2

What would happen if there was a mutation of RTK/Ras/NF1/MAPK?

Answer 2

Ras or NF1 mutation could cause constitutive stimulation of pathway if GTP not hydrolyzed.

Question 3

What is the function of PI3K/PKB-Akt/BAD-P/Bcl2/BAX/CytC?

Answer 3

BAD is pro-apoptotic; Bcl2 is anti-apoptotic. Phosphorylation of BAD allows Bcl2 to bind BAX and inhibits its oligomerization and CytC leaves mitochondrion

Question 4

What is the function of CDK/Rb/E2F?

Answer 4

Rb is a brake. It binds and inhibits E2F transcription factor thus causing pause in the cell cycle.

Question 5

What is the function of P53/p21/Rb/E2F?

Answer 5

P53 is a brake and can also cause apoptosis.

P53 is active with DNA damage. It stimulates p21 expression. P21 is a CKI and it inhibits CDK-cyclin complex.

Question 6

What are the syndromes associated with Rb and TP53 mutations?

Answer 6

The cancer predisposition syndromes; Li Fraumeni if there is a TP53 mutation; Rb mutations can lead to retinoblastoma and other cancers.

Question 7

In cell signaling and apoptosis, what does Bcl2 do?

Answer 7

Bcl2 inhibits BAX oligomerization and is anti-apoptotic.

Question 8

What is oligomerization?

Answer 8

The combining of a few monomers, in a set number, to form an oligomer. An oligomer is different than a polymer in that, in theory, a polymer could have an infinite number of monomers whereas an oligomer has only a particular number.

Question 9

What does p53 do when it finds DNA damage?

Answer 9

With DNA damage, p53 induces Puma which binds Bcl-2, promoting Bcl-2’s dissociation from Bax

Question 10

What happens when BAD is de-phosphorylated?

Answer 10

Unphosphorylated Bad binds Bcl-2 & further inhibits Bcl interaction w/ Bax

Question 11

When Bcl2 can’t interact with Bax, what does Bax do?

Answer 11

Bax oligomerizes & forms a mitochondrial channel.

Question 12

What happens if Bax is able to oligomerize into a mitochondrial channel?

Answer 12

Cyt C leaves the mitochondria and binds to Apaf-1, which initiates a caspase cascade.

Question 13

What happens when a caspase cascade has been initiated?

Answer 13

Substrates are cleaved, apoptosis results

Question 14

What are the three types of cancer genes?

Answer 14

Oncogenes
Tumor suppressor genes
DNA repair/cell cycle genes

Question 15

What are some distinguishing features of a retrovirus tumor (as opposed to a DNA tumor virus)

Answer 15

Retroviruses carry oncogenes picked up from a genome. They are not a significant cause of human cancer as far as we know.

Question 16

What are some distinguishing features of DNA tumor viruses (as opposed to a retrovirus tumor)

Answer 16

There is no ortholog of DNA tumor viruses in human or animal genomes. For example, the T antigen gene of SV40 virus evolved on its own. HPV is a DNA tumor virus and it causes cervical cancer.

Question 17

What are features specific to DNA tumor viruses?

Answer 17

DNA tumor viruses have a DNA genome, they can cause human cancer, and vaccines can help.

Question 18

What are features specific to retroviruses?

Answer 18

Retroviruses have an RNA genome, the transforming gene has a human counterpart, they can integrate into the host genome, and they can be used for gene therapy.

Question 19

Can both retroviruses and DNA Tumor viruses cause animal cancer?

Answer 19

Yes

Question 20

Between oncogenes and tumor suppressor genes, which one is activated by a mutation and which one is inactivated?

Answer 20

Oncogenes are ACTIVATED by mutations.

TSGs are INACTIVATED by mutations.

Question 21

What do tumor suppressor genes and oncogenes have in common?

Answer 21

Both can be involved in cell growth, in both there are somatic mutations associated with cancer.

Question 22

What do oncogenes rarely do that tumor suppressor genes always do?

Answer 22

Have germline mutations associated with cancer, and follow autosomal dominant inheritance.

Question 23

How do we know HPV causes cervical cancer?

Answer 23

DNA sequences of HPV types 16 and 18 (high-risk viral types) are present in 85% of cervical squamous cell carcinomas and high-grade in-situ neoplasia.

Question 24

How does HPV cause cervical cancer?

Answer 24

Viral DNA is integrated into host genome causing disruption of a viral gene that leads to overexpression of the viral oncoproteins E6 and E7.

Question 25

Once the HPV DNA is integrated into the host genome, what do oncoproteins E6 and E7 do?

Answer 25

E6 and E7 proteins bind to p53 and Rb proteins respectively and inactivate them, causing loss of cell cycle control, genomic instability, and transformation to the neoplastic phenotype.

Question 26

What are the three tumor suppressor genes we talked about this week?

Answer 26

p16, p21 and Rb

Question 27

Go through the pathway of what happens when E6 is produced.

Answer 27

E6 binds to p53, preventing it from transcribing p21, performing DNA repair, and from initiating apoptosis.

Question 28

In terms of activating proto-oncogenes, describe what happens with 9:22 reciprocal translocation.

Answer 28

9:22 reciprocal translocation on the Philadelphia chromosome; This causes bcr-abl fusion; It is associated with Chronic Myeloid Leukemia (CML); Treated with imatinib (inhibitor of tyrosine kinase)

Question 29

In terms of activating proto-oncogenes, describe what happens with 8:14 translocation.

Answer 29

8:14 translocation is associated with Burkitt lymphoma; after translocation, c-Myc (a gene for a transcription factor) expression is regulated by IgH promoter and is overexpressed. This results in overexpression of many other genes, including cell proliferation genes.

Question 30

What does it mean that oncogenes are dominant at a cellular level?

Answer 30

It means that a single mutation which will activate the oncogene on only one allele will cause the mutation to be expressed.

Question 31

What are the proto-oncogenes that are often activated and overexpressed in breast cancer? How is that treated?

Answer 31

HER2/neu genes (ErbB protein family) | Treated with monoclonal antibody drug trastuzumab (Herceptin) which targets tyrosine kynase

Question 32

Germline heritable oncogene mutations are rare. What is the important exception for this week?

Answer 32

RET proto-oncogene (gain of function mutation) - Activating point mutations in RET can give rise to the hereditary cancer syndrome known as Multiple Endocrine Neoplasia type 2 (MEN 2). -Associated with medullary thyroid carcinoma, parathyroid tumors, pheochromocytoma RET stands for "rearranged during transfection"

Question 33

Is MEN 2 related to MEN 1?

Answer 33

No, not really. MEN 1 is a mutation of a different gene, which causes a different spectrum of disease. (MEN 2 Is an oncogene, and MEN 1 is a TSG)

Question 34

What are the hallmarks of hereditary predisposition cancers?

Answer 34

``` Earlier age of onset Multiple primaries (and bilateral involvement in paired organs) ```

Question 35

Tumor Suppressor genes are inherited with autosomal dominant genetics but act recessively at the cellular level. What does this mean in plain English?

Answer 35

TS genes are passed through the autosome and sorted like all other genes. However, like autosomal recessive genes, you need two mutated alleles in one cell for that cell to become cancer. If the normal version of that allele mutates at some point, that is called the "second hit" that puts you on the road to cancer. All of this will happen in a single somatic cell, which is why it is referred to as "at the cellular level."

Question 36

Important facts about Retinoblastoma

Answer 36

A form of eye cancer caused by a gene defect in the Rb protein, which is a regulator of the cell cycle. Loss of function of both of these Tumor Suppressor Genes leads to cancer. During early development, retinoblast cells differentiate into cells that fill the eye. If there are two hits on the Rb gene, these cells can continue to divide until they become cancer. You see no red light reflex when you shine light into the eye, because the tumor blocks return of light (Leukocoria) Primarily a pediatric cancer.

Question 37

What might help you differentiate between hereditary and sporadic Retinoblastoma?

Answer 37

In hereditary, the first hit was inherited from a parent and thus is a germ-line mutation. That means the first hit would be present throughout all the retinoblasts in both eye. In sporadic, you would need to randomly develop two distinct "hits". With that in mind I would expect a bilateral (in both eyes) presentation of Retinoblastoma or multiple primary sites of it in one eye to be indicative of the hereditary form (the odds would be so low of getting two somatic mutations to the same cell in each eye simultaneously).

Question 38

Ways you can get a second hit

Answer 38

Somatic mutation of the good allele Lose the locus from an unaffected parent by chromosome loss or by mitotic recombination. Hypermethylation: gene silencing of the good copy via epigenetic change.

Question 39

What is Rb protein and how does it work?

Answer 39

Rb is a brake for cell division. It binds and inhibts E2F transcription factors, causing a pause in the cell cycle. Two hit mutations in it can lead to retinoblastoma and other forms of cancer.

Question 40

TP53 (P53)

Answer 40

The guardian of the genome: - causes cell cycle to pause so DNA damage can be reparaired - also can initiate apoptosis if damaged cell needs to be eliminated - mutation in P53 can cause Li-Fraumaeni syndrome ( a cancer predisposition syndrome)

Question 41

How does P53 work?

Answer 41

When DNA damage is detected, transcription factor P53 is activated: - P53 stimulates transcription of P21, a CDK inhibitor - P21 binds and inactivates a CDK-cyclin complex - Cell is arrested in G-1 until DNA damage is repaired or it dies.

Question 42

Li-Fraumeni Syndrome

Answer 42

Hereditary cancer pre-disposition syndrome that greatly increases the risk of developing cancer. Results from a child receiving a bad copy of the P53 allele. Though P53 is a tumor suppressor gene, Li-Fraumeni phenotype is passed down in an autosomal dominant way because the second hit is virtually inevitable with every cell in the body having the first hit.

Question 43

Li-Fraumeni Syndrome: Presentation and Treatment

Answer 43

Characterized by early onset of cancer/and or multiple different cancers because of inheriting a bad P53 allele. Typically breast, bone, brain, lung, skin, and other cancers. Patient must avoid mutagens like x-rays. They need colonoscopies and other screening exams frequently.