Neoplasia II/III

Question 1

Markers of clonality include…

Answer 1

methylation patterns of specific genes or indicators of identical gene rearrangements (Ig or T cell isotypes)

Question 2

Four classes of genes that are targets for alterations that cause autonomous proliferation of cells

Answer 2

Growth promoting proto-oncogenes
growth-inhibiting tumor suppressor genes
Genes that regulate apoptosis
Genes involved in DNA repair

Question 3

What is transformation?

Answer 3

Attainment of the capacity for autonomous growth

in vitro - can grow without GFs and make colonies that override contact inhibition

Question 4

What is tumor progression?

Answer 4

Growth of a transformed cell from a single cell to a clone of cells to a population with the ability to invade and metastisize

Question 5

Seven fundamental changes in cell physiology that determine malignant phenotype?

Answer 5

1. Self sufficiency in growth signals
2. Insensitivity to growth-inhibitory signals
3. Evasion of apoptosis
4. Defects in DNA repair
5. Limitless replicative potential
6. Sustained angiogenesis
7. Ability to invade and metastasize

Question 6

Progression through the cell cycle is regulated by…

Answer 6

Cyclins and cyclin dependent kinases

Question 7

What does Cyclin D do?

Answer 7

Activates CDK, which P-ates RB, which is an ON-OFF for the cell cycle

Question 8

What does RB do?

Answer 8

Acts as break to inhibit cells from going from G0/G1 into S phase. P-ation of RB causes dissociation of RB from E2F and permits replication.

Question 9

_____ regulates mitotic prophase

_____ regulates nuclear division

Answer 9

Cyclin A/CDK2

Cyclin B/CDK1

Question 10

How does p53 work?

Answer 10

Activates p21 to inhibit replication of damaged cells. If cell can’t be repaired, triggers apoptosis.

Question 11

When can the cell cycle stop damaged cell duplication

Answer 11

G1/S

G2/M

Question 12

G1/S multiplication checkpoint occurs through

Answer 12

p53

Question 13

Mitogenic stimulation in cancer is often associated with…

Answer 13

Constitutively active ras, HER2/neu

Question 14

Most important signal transducing protein to remember?

Answer 14

Ras.
Most common abnormality of dominant oncogenes.
Colon, Pancreas, Thyroid especially

Question 15

Philadelphia Chromosome (CML) is associated with what mutation?

Answer 15

c-abl. Increases in tyrosine kinase activity

Question 16

Most important nuclear regulatory protein to remember? What does it do?

Answer 16

Myc
Immediate early growth response genes.
Assoc. with Burkitt’s and neuroblastoma

Question 17

p53 is especially associated with which cancers?

Answer 17

Colon, breast, lung

Question 18

How does Neurofibromatosis happen

Answer 18

NF-1 enhanced Ras-GTPase to downregulate Ras

Question 19

overexpression of _____ is a common way that cancers may try to turn off apoptosis

Answer 19

bcl-2

Question 20

Four important tumor repair gene mutations..

Answer 20

Herditary non-polyposis cancer syndrome
Xeroderma pigmentosum
ataxia-telangiectasia/Bloom Syndrome/Fanconi anemia
BRCA1 and 2

Question 21

Name the two families of CDK inhibitors

Answer 21

CIP/KIP – they have p21

INK4/ARF – act on CDK4/CycD

Question 22

The G2/M checkpoint is especially important in….

Answer 22

cells exposed to ionizing radiation

Question 23

Two main mechanisms for altered expression of oncogenes following translocation

Answer 23

1. Swapping of gene regulatory elements to allow transcription of a quiescent gene
2. Formation of abnormal chimeric proteins

Question 24

Chromosomal changes are especially associated with what kind of cancers?

Answer 24

Leukemias

Question 25

How might epigenetic changes alter cancer development

Answer 25

DNA methylation silences gene expression, demethylation expresses normally silenced genes