ASF - Neoplasia (Lewin)

Question 1

What is a promotor and how can it lead to carcinogenesis?

Answer 1

Promotor - region of DNA that is involved in cell proliferation

Chemical carcinogens can cause mutations of promotor regions of DNA to induce unregulated cell proliferation, which leads to neoplasia

Question 2

Which toxin is associated with urothelial carcinoma of the bladder?

Answer 2

Naphthylamine (form cigarette smoke)

Question 3

What is p53 and what happens when it is deleted?

Answer 3

p53 is a DNA stabilization protein that binds to damaged DNA. It stops the cell cycle, regulates apoptosis, and induces production of p21 (involved in DNA repair) and allows DNA repair before cell cycle continues

Deletion of p53 leads to uninhibited cell proliferation and propagation of mutated DNA

Question 4

Differentiate between the inherited and sporadic forms of retinoblastoma.

Answer 4

• Inherited form
  
  • One germ-line mutation passed from parent (present in all cells)
  • Second hit - spontaneous somatic cell mutation in retinal cell
• Sporadic form
  
  • Two normal alleles become mutated after birth in somatic cells of the eye

Question 5

Which cancers are associated with asbestos?

Answer 5

Lung cancer and mesothelioma

Question 6

UV radiation is responsible for the induction of what types of cancers?

Answer 6

Melanoma, squamous cell carcinoma, and basal cell carcinoma

Question 7

Overproduction of KiT is associated with which cancer?

Answer 7

Gastrointestinal stromal tumor

Question 8

What antigen is overexpressed in some breast and ovary cancers?

Answer 8

Her2/neu

Question 9

Underglycosylation of a cell membrane can express some foreign epitopes. Give an example, and with what cancers is it assoicated?

Answer 9

MUC-1

MUC-1 is normally hidden under mucins, and is protected from immune reactions. Lack of mucus decreases this protection and unmasks MUC-1, causing an immune response

Associated with: pancreas, ovary, and breast cancer

Question 10

Alkylating agents are associated with which types of cancers?

Answer 10

Lymphomas and leukemias

These cancers arise secondary of alkylating drugs used as chemo for a primary cancer treatment.

Question 11

Overexpression of ____ is associated with MEN2A, MEN2B, and medullary carcinoma of the thyroid.

Answer 11

RET gene

Question 12

What toxin is associated with angiosarcoma of the liver?

Answer 12

Vinyl chloride

Question 13

What is the pathogenesis of follicular cell lymphoma?

Answer 13

Follicular cell lymphoma is caused by a t(14:18), which increases levels of Bcl-2. Bcl-2 is an anti-apoptotic factor that inactivates caspases, which decreases apoptosis and leads to hyperproliferation of cells.

Question 14

Arsenic is associated with which cancers?

Answer 14

Squamous cell carcinoma of skin, lung cancer, and angiosarcoma of liver

Question 15

Overexpression of n-myc is associated with what type of tumor?

Answer 15

Neuroblastoma

Question 16

Alcohol is associated with which types of cancers?

Answer 16

Oropharyngeal, upper esophageal, hepatocellular carcinoma and pancreatic carcinoma

Question 17

Overexpression of what GF receptor leads to the formation of breast cancer?

Answer 17

Her2/neu

Question 18

Burkitt Lymphoma is associated with which translocation?

Answer 18

t(8:14)

Translocation of c-myc (from chromosome 8) to Ig heavy chain gene (on chromosome 14)

Question 19

What are the two components of Knudson’s two-hit hypothesis

Answer 19

1. First hit - inherited germline mutation from parent –> mutation present in all cells
2. Second hit - spontaneous mutation of second allele –> disease phenotype

Typically involved in tumor suppressor gene mutations, which require both alleles to be mutated to cause cancer (ex: retinoblastoma)

Question 20

What is the concept of multistep carcinogenisis?

Answer 20

The notion that carcinogenesis takes multiple steps before it becomes a malignant threat

Question 21

What are examples of direct-acting alkylating agents? What are they typically used for?

Answer 21

Cyclophosphamide, chlorambucil, nitrosureas

Used as chemotherapeutic agents

Question 22

Helicobacter pylori is most commonly associated with what type of cancer?

Answer 22

MALT lymphoma and gastric lymphoma

Question 23

Breast cancer associated with an over-expression of Her2/neu is treated by?

Answer 23

Trastuzumab

Question 24

How do indirect chemical agents work as carcinogens?

Answer 24

Indirect carcinogens must be converted into an active carcinogen by phase I liver enzymes before it can cause mutations

Question 25

Overexpression of cyclin D1 is associated with what type of cancer?

Answer 25

t(11:14)

Cyclin D gene translocated to Ig heavy chain gene –> upregulation of cyclin D

High levels of cyclin D promotes G1 to S phase in cell cycle

Question 26

True or False: Curing a patient of Helicobacter pylori will eliminate their induced MALT-lymphoma.

Answer 26

True