Cancer

Question 1

Where can oral and oropharyngeal cancers occurs most often?

Answer 1

Tongue , Tonsils, Oropharynx , Gums, Floor of Mouth

Question 2

What kind of carcinomas are almost all oral cancers?

Answer 2

Squamous Cell Carcinoma

Question 3

What is carcinoma in situ? How is it different from invasive squamous cell cancer?

Answer 3

The earliest form of squamous cell cancer that is still at the epithelium. Invasive cancer will have grown deeper into the layer of the oral cavity or oropharynx

Question 4

What infections cause most of the squamous cell cancers of the oropharynx? Is it the same for the oral cavity?

Answer 4

Certain high-risk types of HPV can cause cancer in the oropharynx but is rarely related to the oral cavity.

Question 5

What is the prognosis of HPV positive vs negative cancers?

Answer 5

HPV positive related cancers have a better outcome than squamous cell cancers that are HPV-negative

Question 6

What are the two major classes of genes involved in tumorigensis?

Answer 6

Tumor Suppressor Genes and Oncogenes

Question 7

What do oncogenes do in relation to cell proliferation? What is cell activity like in these cells?

Answer 7

Oncogenes promote cellular proliferation by up-regulation in tumor cells.

Question 8

What do tumor suppressor genes do? What is cell activity like in these cells?

Answer 8

Tumor Suppressor Genes are supposed to negatively regulate cellular proliferation. In tumor cells, this gene is down regulated.

Question 9

Cancer requires ______ and _____ to proceed.

Answer 9

Activation of oncogenes and inactivation of tumor suppressor genes

Question 10

Where do mutations occur for oncogenes? What kind of mutations occur?

Answer 10

Oncogenes are mutated at the SAME amino acid position. Missense mutations are common.

Question 11

Where do mutations occur for tumor suppressor genes? What kind of mutations occur?

Answer 11

TSG’s can be mutated through the protein length. Nonsense and frameshift mutations are most common.

Question 12

What are the 3 pathways that can lead to cancer?

Answer 12

Cell Fate , Cell Survival and Genome Maintainence

Question 13

Describe cell fate. What is favored?

Answer 13

Genetic alternation results in proliferation being favored over differentiation of cells. The accumulation of undifferentiated cells can make them malignant.

Question 14

Describe Cell Survival. What allows the cancer cell to flourish?

Answer 14

Cancer cells divide abnormally as is due to autonomous alternations but surrounding healthy cells cannot keep up. As a result, cancer cells will grow too quickly, depleting nutrients. Cancer cells will develop a mutation that will activate growth even without Growth Factor

Question 15

Describe genome maintenance.

Answer 15

Mutations in DNA repair factors can act by accelerating the acquisition of mutations that function through process of cell fate and survival.

Question 16

What is commonly found over-expressed in epithelial tissue? How can it cause cancer?

Answer 16

Epidermal Growth Factor Receptor - Tyrosine Kinase.

Normally the EGFR required GF to activate but mutations can allow for the EGFR to induce proliferation withOUT the ligand (ligand independent firing).

Question 17

Describe the RAS mutation. Is it a tumor suppressor gene or an oncogene?

Answer 17

RAS is responsible for producing GTPases that are required to turn GTP into GDP to render the protein inactive. The RAS mutation causes is a single-nucleotide change at particular residues that stops it from turning GTP to GDP thus making the cell divide uncontrollably. RAS is an ONCOGENE.

Question 18

What is the most common RAS mutation?

Answer 18

G12V (missense)

Question 19

Describe FAT1 mutation. Is it a tumor suppressor gene or an oncogene?

Answer 19

FAT1 normally negatively regulates proliferation and drives differentiation. When active, it shuts off YAP/TAZ via a series of messengers that allows differentiation to occur instead. When mutated, FAT1 has a loss of function which allows YAP/TAZ to move forward with proliferation instead. FAT1 is a TUMOR SUPPRESSOR GENE.

Question 20

What happens the 3 phases of the cell cycle? What serves as checkpoints for each phase?

Answer 20

G1 - Growth
S- DNA replication
G2-Chromosome Segregation

Eventually leading to mitosis. CDK or cyclin dependent kinases control the cell cycle by phosphorylating factors to allow for progression from one phase to the next.

Question 21

Describe the CDKN2A mutation. What is another name for this gene. Is it a tumor suppressor or activator?

Answer 21

CDKN2A normally is induced when a cell needs to exit the cycle. The checkpoint also known at p16 is found between G1 and S. When mutated, CDKN2A/p16 is down-regulated thus allowing for cell proliferation. CDKN2A is a TUMOR SUPPRESSOR gene.

Question 22

What are the 6 characteristics of apoptosis?

Answer 22

1. Outer membrane blebbing
2. Shrinking
3. Condensation of nucleus
4. Fragmentation of chromosomes
5. Formation of cytoplasmic vacuoles
6. Cell fragments generated via apoptosis are often swept up by other cells and phagocytes.

Question 23

How is apoptosis signaled via the extrinsic pathway?

Answer 23

Death receptors are present on cells that induce the formation of DISC (death-inducing signal complex) when signaled. This recruits pro-caspase 8 and self-cleavage of caspase-8. The cleavage of the caspase-8 can activate caspase 3,6 and 7 causing destruction of cellular proteins.

Question 24

Where is Cytochrome C released from ?

Answer 24

Mitochondrial Inner Membrane Space

Question 25

How is apoptosis signaled via the intrinsic pathway ? Define the big event!

Answer 25

Mitochondrial Outermembrane Permeabilization

This causes the release of Cytochrome C from the mitochondrial inner-membrane space. Cytochrome C activates a complex between Caspase 9 and APAF1 via the Caspase Recruiting Domain of APAF1.

This releases AIF and Endonuclease G which degrades DNA. Caspase 9 also recruits Caspase 3,6 and 7.

Question 26

What is APAF1

Answer 26

apoptosis protease activating factor

Question 27

What is recombination? What are its two functions?

Answer 27

Recombination is the exchange of genetic information.

1. It can be used to repair double strand damage to chromosomes by using information from the homologous chromosome.
2. Shuffle genetic information to allow for re-distrubution of parent traits.

Question 28

What enzyme widens the break to the gap?

Answer 28

Exonuclease

Question 29

What may happen to sequences during the recombination process?

Answer 29

Repairs are often done in non-coding regions so usually it is okay!

Question 30

What enzyme allows for recombination?

Answer 30

Recombinase

Question 31

____________ synthesizes the broken strands.

Answer 31

DNA polymerase

Question 32

___________ glues the strands

Answer 32

Ligase

Question 33

__________ Separates each chromosome back

Answer 33

Resolvase

Question 34

What does the loss of BRCA2 contribute too?

Answer 34

DNA loss and genomic instability

Question 35

What is the most frequently mutated gene that causes oral cancers?

Answer 35

p53

Question 36

How does the p53 gene cause cancer? Is it a tumor suppressor gene or an oncogene?

Answer 36

If DNA damage is present in a cell, induction of p53 will normally arrest the cell cycle and attempt to fix the DNA damage and continue proliferating OR subject the cell to apoptosis if the damage is too beyond repair. In cancer cells lacking p53, there is no cell cycle arrest which can lead to two outcomes. One, the DNA damage may just kill the cell OR continued mutation, selection and tumor evolution can result in cancer.

It has qualities of BOTH a tumor suppressor gene and oncogene! Along with nonsense and frameshift mutations, there is a high number of missense mutations.

Question 37

___________ is a transcription factor that ____________ genes that ____________ regulate proliferation in response to stress

Answer 37

p53, up-regulates, negatively

Question 38

What treatments are available for oral cancer?

Answer 38

Surgery
Radiation Therapy
Chemotherapy
Targeted Therapy
Immunotherapy

Question 39

What is required during surgical treatment of oral cancer?

Answer 39

A negative margin; there is no trace of cancer in the margin’s healthy tissue. Surgeons will often remove the tumor as well as some healthy tissue to ensure this.

Question 40

Describe radiation therapy

Answer 40

High-energy x-rays are used to destroy cancer cells. There are often a set number of appointments.

Question 41

Describe Chemotherapy. Is it specific?

Answer 41

Drugs are used to stop cancer cells from growing and dividing but can block DNA replication and induce DNA damage.

Question 42

What can targeted therapy attack?

Answer 42

A cancer’s specific genes, proteins or tissue environment that contributes to cancer growth and survival.

Question 43

Do all tumors have the same targets? What is the current target antibodies are using in tandem with radiation therapy for head and neck cancers?

Answer 43

No!

Antibodies currently target the EGFR (epidermal growth factor receptor) to prevent dimerization of GF

Question 44

What are immunotherapies?

Answer 44

They use the body’s natural defense to fight cancer by improving body’s ability to attack cancer cells.

Tumor cells can prevent T-lymphocyte activation. However, these immunotherapies can block the interaction between the tumor cell and the t-cell to allow for cell killing.