Pathoma Chapter 3B

Question 1

Proto-oncogenes are essential to?

Answer 1

cell growth and differentiation;

Question 2

mutations of proto-oncogenes form

Answer 2

oncogenes that lead to unregulated cellular growth.

Question 3

Categories of oncogenes include

Answer 3

growth factors, growth factor receptors, signal transducers, nuclear regulators, and cell cycle regulators

Question 4

Growth factors induce

Answer 4

cellular growth (e.g PDGFB in astrocytoma),

Question 5

Growth factor receptors

Answer 5

mediate signals from growth factors (e.g. ERBB2 HER2/neu in breast cancer).

Question 6

What do signal tranducers do?

Answer 6

Relay receptor activation to the nucleus (eg. ras)

Question 7

Ras is associated with

Answer 7

growth factor receptors in an inactive GDP-bound state.

Question 8

Aflatoxins

Answer 8

Hepatocellular carcinoma Derived from Aspergillus, which can contaminate stored grains

Question 9

Alkylating agents

Answer 9

leukemia/lymphoma side effect of chemotherapy

Question 10

Alcohol

Answer 10

Squamous cell carcinoma of oropharynx and upper esophagus, pancreatic carcinoma, and hepatocellular carcinoma

Question 11

Arsenic

Answer 11

Squamous cell carcinoma of skin, lung cancer, and angiosarcoma of liver. Arsenic is present in cigarette smoke.

Question 12

Asbestos

Answer 12

Lung carcinoma and mesothelioma. Exposure to asbestos is more likely to lead to lung cancer than mesothelioma.

Question 13

Cigarette smoke

Answer 13

Carcinoma of oropharynx, esophagus, lung, kidney, and bladder. Most common carcinogen worldwide; polycyclic hydrocarbons are particularly carcinogenic.

Question 14

Nitrosamines

Answer 14

Stomach carcinoma, Found in smoked foods, responsible for high rate of stomach carcinoma in japan

Question 15

Naplithylamine

Answer 15

Urothelial carcinoma of bladder. Derived from cigarette smoke

Question 16

Vinyl chloride

Answer 16

Angiosarcoma of liver, occupational exposure; used to make polyvinyl chlurkle (PVC) for use in pipes

Question 17

Nickel, chromium, beryllium, or silica

Answer 17

Lung carcinoma Occupational exposure

Question 18

Oncogenic viruses

Answer 18

EBV, HHV-8, HBV and HCV, HTLV-1, High-risk HPV

Question 19

EBV

Answer 19

Nasopharyngeal carcinoma, Burkitt lymphoma and CNS lymphoma in AIDS

Question 20

HHV-8

Answer 20

Kaposi sarcoma

Question 21

HBV and HCV

Answer 21

Hepatocellular carcinoma

Question 22

HTLV-1

Answer 22

Adult T-cell leukemia/lymphoma

Question 23

High-risk HPV (e.g. subtypes 16, 18, 31, 33)

Answer 23

Squamous cell carcinoma of vulva, vagina, anus, and cervix; adenocarcinoma of cervix

Question 24

Ionizing radiation

Answer 24

(nuclear reactor accidents and radiotherapy) AML, CML and papillary carcinoma of the thyroid. Generates hydroxyl free radicals.

Question 25

Non Ionizing (UVB sunlight is most common source)

Answer 25

Basal cell carcinoma, squamous cell carcinoma, and melanoma of skin

Question 26

Non Ionizing radiation results in?

Answer 26

formation of pyrimidine dimers in DNA, which are normally excised by restriction endonuclease

Question 27

Ras Receptor binding causes

Answer 27

GDP to be replaced with GTP, activating ras.

Question 28

What does activated ras do?

Answer 28

sends growth signals to the nucleus

Question 29

How is Ras deactivated?

Answer 29

inactivates itself by cleaving GTP to GDP; this is augmented by GTPase activating protein

Question 30

Mutated ras

Answer 30

inhibits the activity of GTPase activating protein. This prolongs the activated state of ras, resulting in increased growth signals.

Question 31

Cell cycle regulators mediate what?

Answer 31

progression through the cell cycle (e.g. cyclin and cyclin-dependent kinase).

Question 32

Cyclins and cyclin-dependent kinases (CDKs) do what?

Answer 32

form a complex which phosphorylates proteins that drive the cell through the cell cycle.

Question 33

The cyclin D / CDK4 complex does what?

Answer 33

phosphorylates the retinoblastoma protein, which promotes progression through the G-S checkpoint

Question 34

What do tumor supressor genes do?

Answer 34

Regulate cell growth decreasing (suppress) the risk of tumor formation;

Question 35

What are some classic examples of tumor supressor genes?

Answer 35

p53 and Rb (retinoblastoma)

Question 36

What does p53 regulate?

Answer 36

progression of the cell cycle from G to S phase

Question 37

In response to DNA damage, what does p53 do?

Answer 37

slows the cell cycle and upregulates DNA repair enzymes.

Question 38

PDGFB

Answer 38

Platelet-derived growth factor, overexpression, autocrine loop, astrocytoma

Question 39

FRBB2 [HER2f neu]

Answer 39

Epidermal growth factor receptor, Amplification mechanism, Subset of breast carcinomas

Question 40

RET

Answer 40

Neural growth factor receptor, Point mutation MEN 2A, MEN 2B and sporadic medullary carcinoma of thyroid

Question 41

KIT

Answer 41

Stem cell growth factor receptor, Point mutation, Gastrointestinal stromal tumor

Question 42

RAS gene family

Answer 42

GTP-binding protein, Point mutation, Carcinomas, melanoma, and lymphoma

Question 43

ABL

Answer 43

Tyrosine kinase T(9;22) with BCR CML and some types of ALL

Question 44

What are the nuclear regulators?

Answer 44

C-MYC, N-MYC, L-MYC

Question 45

c-MYC

Answer 45

Transcription factor, t(8;I4) involving IgH, Burkitt lymphoma

Question 46

N-MYC

Answer 46

Transcription factor, Amplification, Neuroblastoma

Question 47

L-MYC

Answer 47

Transcription factor, Amplification, Lung carcinoma (small cell)

Question 48

CCND1 (cyclin D1)

Answer 48

Cyclin t(8;14) involving IgH, Mantle cell lymphoma

Question 49

If DNA repair is not possible, what does p53 do?

Answer 49

induces apoptosis.

Question 50

How does p53 induce apoptosis?

Answer 50

upregulates BAX, which disrupts Bcl2 leading to cytochrome c leaks from the mitochondria activating apoptosis