Neoplasm V

Question 1

What does a translocation of the BCL-2 genes from chromosome 14to 18 do?

Answer 1

Causes an overexpression of BCL-2 leading to prevention of B-lymphocyte apoptosis.
This ultimately leads to follicular lymphoma.

Question 2

What happens if the APC gene is over expressed?

Answer 2

Prevents nuclear transcription leading to colorectal cancer.

Question 3

What is the p53 gene responsible for and what cancer is it associated with?

Answer 3

Normally transcribes p21 (blocks g->S phase)

Li Fraumeni syndrome.

Question 4

What is the Rb gene responsible for and what cancer is it associated with?

Answer 4

Tumor supressor gene that normally inhibits E2F (Blocks G to S phase)

Retinoblastoma, osteosarcoma, and soft tissue sarcoma.

Question 5

What is the VHL gene responsible for and what cancer is it associated with?

Answer 5

Inhibits HIF1a and leads to Von Hippel-Lindau syndrome.

Question 6

The APC gene and B-catenin are components of what pathway?

Answer 6

WNT signalling pathway controlling cell fate, and cell polarity during embryonic development.

Also controls tisue proliferation in the adult bone marrow, skin, and intestine.

Question 7

What is the WNT pathway in control of?

Answer 7

Tissue proliferation, adult bone marrow, skin and intestine.

Question 8

How does P53 work?

Answer 8

P53 activates BAX leading to apoptosis in the event that the damaged cell is not fixed.

It activates P21 leading to G1 arrest

P51 also activates GADD45 which is a DNA repair mechanism.

Question 9

How does HPV E6 and HPV E7 effect the cell cycle?

Answer 9

E6 down regulates p53 leading to lack of BAX production.

E7 inactivates p21 leading to lack of cell cycle arrest.
It also inactivates RB leading to lack of cell cycle arrest.

Question 10

What cancer is related to the Rb gene?

Answer 10

Retinoblastoma
Osteosarcoma
Soft tissue Sarcoma

Question 11

What is Knudson’s two hit hypothesis?

Answer 11

Both alleles of Rb locus must be inactivated thus, two hits are required!
Typically the first hit is through the germ line inheritance, the second can be a random mutation.

Question 12

What is the VHL gene for?

Where is it found?

Answer 12

Tumor suppresor gene located on chromosome 3p and is part of the ubiquitin ligase complex.

Regulates nuclear transcription via HIF-1a

Question 13

What disease is caused by a VHL gene mutation?

Answer 13

VHL syndrome leading to:
Hereditary renal cell carcinomas
Pheochromocytomas
Hemangioblastomas of CNS
Retinal angiomas
Renal cysts

Question 14

What is the Warburg effect?

Answer 14

Cancer cells have an affinity for glucose and convert it to lactos via the glycolytic pathway.

Question 15

What is a PET scan?

Answer 15

Pt injected with 18F-fluorodeoxyglucose that only cancerous cells can take up, allows for visualization of the tumor.

Question 16

What are epigenetic changes?

Answer 16

Methylation of gens resulting in a change in expression without mutation.

Question 17

What is P-glycoprotein?

Answer 17

MDR1 Multidrug resistant protein, serves as a tool for tumor cells to evade chemotherapy.

Question 18

What are lamellated calcified spherule Psammoma bodies most commonly seen in?

Answer 18

Concentric lamellated calcified spherules seen in:

Papillary thyroid carcinoma

Question 19

What are chemical carcinogens and how do they act?

Answer 19

Highly reactive electrophiles that steal electrons causing cell damage.

Are:
Direct acting: Act without modificaton
Indirect acting: Require metabolic activation.

Question 20

Give some examples of direct acting carcinogens

Answer 20

Chlorambucil
Busulfan
Melphalan

Question 21

Give some examples of Indirect caricinogens

Answer 21

Polycyclic aromatic hydrocarbons found in cigaret smoke.

Effect the liver!

Question 22

Where does B-Naphthylamine effect?

Answer 22

Causes bladder cancer and is heavily exposed in workers that deal with aniline dye and rubber industries.

Question 23

What is Alfatoxin B1?

Answer 23

IS a fungus mycotoxin causing hepatocellular carcinoma due to p53 mutations.

Question 24

What is Nitrosamines?

Answer 24

Causes Gastric cancer from reaction of nitrostable amines and nitrite in the stomach.

Nitrite is produced from nitrate and used as a preservative.

Question 25

What sort of cancer promotion does Estrogen cause?

Answer 25

Promotes liver tumors.

Question 26

What sort of cancer promotion does Diethyl-stilbesterol cause?

Answer 26

Post menopausal endometrial cancer, vaginal cancer in offspring exposed in utero.

Question 27

What sort of cancer is caused by high dietary fat?

Answer 27

High fat causes increased bile leading to colon cancer.