Neoplasia - 4

Question 1

Examples of tumors with frequent p53 mutations (2)

What does this allow them to be resistant to

Answer 1

Examples: lung and colorectal cancers

Allows resistance to irradiation and chemotherapy

Question 2

Germline mutations at 5q21 are associated with what disease?

Answer 2

APC (5q21)

Familial adenomatous polyposis

Question 3

Germline mutation at 3p are associated with what disease?

Answer 3

VHL (3p)
VHL - hereditary renal cell cancers, pheochromocytomas, hemangioblastomas of the central nervous system, retinal angiomas, and renal cysts

Question 4

What kind of complex is VHL protein a part of?

What is the critical substrate involved in this complex?

Answer 4

VHL is part of a ubiquitin ligase complex

Critical substrate: HIF1α (hypoxia-inducible transcription factor 1α)

Question 5

In a hypoxic environment HIF1α translocates to the nucleus and turns on genes for which growth factors?

Answer 5

VEGF and PDGF

Question 6

Mutation of 11p13 are associated with what disease?

Answer 6

Wilm’s tumor

Question 7

WT1 protein is a transcriptional activator of genes involved with what?

Answer 7

renal and gonadal differentiation.

Question 8

BCL2 gene family is located on what chromosome?

What is the function of the gene products produced?

Answer 8

Chromosome 18

Function: prevent mitochondrial (mt) leakage of cytochrome c

Question 9

t(14;18) in B cells results in what action?

What disease is this associated with?

Answer 9

Results in overexpression BCL2 protein product

Associated with follicular lymphoma

Question 10

In 85% - 95% of tumors there is upregulation of what enzyme?

What does this result in?

Answer 10

Telomerase

Limitless Replicative Potential

Question 11

Describe tumor vasculature

Answer 11

The vessels are leaky and dilated, and have a haphazard pattern of connection

Question 12

Tumors remain in a stage of vascular quiescence (small or in situ) for years until what event occurs?
What is the molecular basis for this event?

Answer 12

Angiogenic switch

Molecular basis: involves increased production of angiogenic factors and/or loss of angiogenic inhibitors

Question 13

What two phases is the metastatic cascade divided into?

Answer 13

invasion of the extracellular matrix (ECM)

vascular dissemination, homing of tumor cells, and colonization.

Question 14

Steps involved in the first phase of metastatic cascade?

Answer 14

Changes (“loosening up”) of tumor cell-cell interactions
Degradation of ECM
Attachment to novel ECM components
Migration of tumor cells

Question 15

When does genomic instability occur?

What are 3 types of DNA-repair systems?

Answer 15

when both copies of the DNA repair gene are lost
DNA repair systems:
mismatch repair 
nucleotide excision repair 
recombination repair

Question 16

HNPCC/Lynch Syndrome:

a. affect what anatomical location predominantly
b. results from defects in genes involved with which kind of DNA repair system?
c. Hallmark
d. genes involved in pathogenesis

Answer 16

a. familial carcinomas of the colon affecting predominantly the cecum and proximal colon
b. DNA mismatch repair
c. microsatellite instability
d. MSH2 , MLH1

Question 17

Xeroderma pigmentosum:

a. results from defects in genes involved with which kind of DNA repair system?
b. Puts you at increased risk at an early age for what cancers?
c. cross linking of what prevents normal DNA replication in this disease?; what is the inciting stimulus?

Answer 17

a. nucleotide excision repair system.
b. skin cancers (basal cell carcinoma, squamous cell carcinoma, and malignant melanoma
c. cross linking of pyrimidine residues; UV radiation

Question 18

List diseases with defects in DNA repair by Homologous Recombination (3)
What is their common mode of inheritance?

Answer 18

Diseases:
Fanconi anemia
Ataxia telangectasia
Bloom syndrome
Autosomal recessive

Question 19

Hypersensitivity to DNA cross linking agents is seen in associated with what disease?
What does this put you at an increased risk of?

Answer 19

Fanconi anemia

developing malignant lymphomas, squamous cell carcinoma, and hepatocellular carcinomas; assoc with bone marrow aplasia

Question 20

a. Mutation in gene ATM is associated with what disease?
b. What role does this gene usually play?
c. What does this mutation predispose people to?

Answer 20

a. Ataxia Telangectasia
b. important in recognizing and responding to DNA damage caused by ionizing radiation
c. malignant lymphomas and exhibit neural defects

Question 21

Bloom syndrome:

a. what does the defective gene encode for?
b. what process does this defective gene product participate in (in terms of ionizing radiation)?
c. What does this mutation predispose people to?

Answer 21

a. A Helicase
b. participates in DNA repair by homologous recombination; – hypersensitivity to ionizing radiation
c. cancers such as gastrointestinal tumors and malignant lymphomas, developmental defects

Question 22

a. what is the “eighth hallmark of cancer”?
b. explain this mechanism
c. what imaging technique would be used to visualize this?; what is being visualized?

Answer 22

a. Warburg effect
b. Even in the presence of ample oxygen, cancer cells shift their glucose metabolism away from the oxygen hungry, but efficient, mitochondria to glycolysis
c. PET scan; “glucose hunger” –> most tumors are PET positive but rapidly growing ones are markedly so

Question 23

Translocation (9,22)

Answer 23

Chronic myelogenous leukemia (CML)

Question 24

Translocation (8,21), (15,17)

Answer 24

Acute myeloid leukemia (AML)

Question 25

Translocation (8,14)

Answer 25

Burkitt lymphoma

Question 26

Translocation (11,14)

Answer 26

Mantle cell lymphoma

Question 27

Translocation (14,18)

Answer 27

Follicular lymphoma

Question 28

Translocation (11,22)

Answer 28

Ewing sarcoma

Question 29

a. Explain molecular basis of Multistep Carcinogenesis

b. What is a classic example of this

Answer 29

a. stepwise accumulation of multiple mutations that act in complementary ways to produce a fully malignant tumor
b. colon carcinoma