Molecular Basis of Neoplasia

Question 1

What are the three typical ways in which a proto-oncogene may become an oncogene?

Answer 1

Mutation (insertion, deletion, point), gene rearrangement (translocation), gene amplification

Question 2

What are the most important cell cycle regulators mutated in cancers that disrupt the cell cycle?

Answer 2

Cyclin D-CDK4/6

Question 3

True/False. Increased production of growth factors is enough for neoplastic transformation.

Answer 3

False. Other mutations or function gains must take place, such as promotion of cell division or inhibition of cell death.

Question 4

True/False. Oncogenes are genetically dominant.

Answer 4

True. The presence of one abnormal allele will override expression of the normal allele.

Question 5

What genes promote apoptosis?

Answer 5

Bax, bad, bid

Question 6

What oncogene is expressed in a large number of human tumors and promotes autocrine growth?

Answer 6

c-sis-proto-oncogene (PDGF-B)

Question 7

What genes are responsible for DNA mismatch repair and are mutated in some cancers?

Answer 7

MSH2, MLH1

Question 8

What growth factor receptor is expressed in a large majority of breast cancers?

Answer 8

HER2

Question 9

The loss of this gene in some cancers causes overstimulation of the PI3K/AKT pathway.

Answer 9

PTEN

Question 10

Nearly all growth factor receptors, when bound by a ligand or mutated, act via what mechanism?

Answer 10

Tyrosine kinase

Question 11

What two genes are highly associated with breast and ovarian cancers?

Answer 11

BRCA-1 & BRCA-2

Question 12

What is the phenomenon haploinsufficiency?

Answer 12

Some cancers may occur without mutations of tumor suppressor genes. In these cases, protein expression of these genes may be reduced, thus disrupting the homeostatic balance

Question 13

What gene is overexpressed in follicular B cell lymphoma to prevent apoptosis?

Answer 13

BCL2

Question 14

What is Lynch Syndrome?

Answer 14

Colon cancer due to failed DNA mismatch repair

Question 15

What gene mutation is associated with Familial Adenomatous Polyposis and non-familial colorectal carcinomas?

Answer 15

APC - functions in the Wnt pathway. Mutation inhibits B-catenin degradation

Question 16

What mutation is the single most common abnormality of dominant oncogenes?

Answer 16

Ras gene mutations - Ras remains phosphorylated and transcription factors are continuously activated

Question 17

True/False. TGF-B acts only as a tumor suppressor that inhibits the cell cycle and promotes apoptosis.

Answer 17

False. While this is true during early cancer development, TGF-B is known to promote tumor proliferation as development continues.

Question 18

What is Xeroderma pigmentosum?

Answer 18

Skin cancer caused by a failure to repair thymine dimers due to skin exposure. Associated with MSH2 & MLH1 mutation

Question 19

What is the most common mutated tumor suppressor gene?

Answer 19

p53

Question 20

Chronic Ras activation is associated with what gene mutation?

Answer 20

NF-1

Question 21

What enzyme has led to the immortalization of some tumor cells?

Answer 21

Telomerase

Question 22

What are oncogenes?

Answer 22

Mutated forms of proto-oncogenes that gain function and promote the cell proliferation and/or inhibit cell death.

Question 23

Mutation of Cyclin D-CDK4/6 casues…?

Answer 23

G1 progression to S phase of the cell cycle. Once the cell enters the S phase, entry into the cell cycle is irreversible

Question 24

What are the normal functions of BRCA-1 & 2?

Answer 24

Double strand DNA break repair

Question 25

True/False. Both alleles of tumor suppressor genes must be mutated in order for a loss of function.

Answer 25

True. A single mutation may increase risk of cancers, but the gene still maintains tumor suppressor function.

Question 26

What disorder is caused by a rare autosomal dominant mutation of p53?

Answer 26

Li Fraumeni Syndrome

Question 27

What two cancers are associated with MSH2 & MLH1 mutations?

Answer 27

Xeroderma pigmentosum & Lynch Syndrome

Question 28

A mutation of what gene causes dysregulation of Cyclin D-CDK4/6?

Answer 28

p16 / INK4a gene

Question 29

What is the normal function of Rb?

Answer 29

When hypophosphorylated, Rb binds E2F to inhibit the cell cycle. Hyperphosphorylation of Rb causes it to break away from E2F and promote entry into the cell cycle. This occurs in some cancers

Question 30

What gene is activated by p53 to inhibit Cyclin E and halt the cell cycle?

Answer 30

p21

Question 31

True/False. Epigenetic factors can result in cancer.

Answer 31

True. Hypermethylation, especially of tumor suppressor genes, can cause cancer.

Question 32

What disorder is associated with PTEN mutation?

Answer 32

Cowden Syndrome

Question 33

What is one of the most common transcription factors abnormally expressed in cancer?

Answer 33

Myc