Genomic Instability

Question 1

Genomic Instability

Answer 1

Changes in a cell’s DNA that make additional changes more likely. ex: gatekeeper mutation

Question 2

Mutagen/Carcinogen starts neoplasia by creating a mutation that is not fatal to the cell but instead give the cell a(n) ________.

Answer 2

advantage

Question 3

Features of Neoplasia: Uncontrolled replication

Answer 3

• Growth in response to new signals, or autonomously (ONCOGENES)
• Loss of usual checks on growth (LOSS OF TUMOR SUPPRESSORS). Including loss of contact inhibition

Question 4

Features of Neoplasia: Immortality

Answer 4

• Disruption of apoptosis

- Activation of telomerase

Question 5

Features of Neoplasia: Loss of DNA repair

Answer 5

Gatekeeper mutations

Question 6

There is good evidence that the metastatic sub-clone changes to become more like a __________ cell.

Answer 6

mesenchymal

Question 7

Neoplasia starts strictly monoclonal or polyclonal?

Answer 7

monoclonal

Question 8

By implication, then, benign tumors are those which acquire features of a neoplasm, but the level of genomic instability is ______________.

Answer 8

markedly less

Question 9

True or False? Treatment Implications from Genomic Instability: The Different Subclones May Respond to TOTALLY Different Chemotherapy Regimens!

Answer 9

True

-ex: KRAS gene

Question 10

Most chemotherapeutics ________ mutations

Answer 10

INCREASE (remember more ways down the pyramid than up)

Question 11

Targeted chemotherapy can…

Answer 11

reduce the chance of additional mutation

Ex: CML –> Lowers rate of replication, and slows additional genomic instability

Question 12

Macro genomic instability:

Answer 12

Chromosomal instability

Question 13

Micro genomic instability:

Answer 13

Nucleotide instability

Question 14

Alterations that make changes at the level of chromosomes more likely

Answer 14

macro genomic instability

Question 15

examples of macro instability

Answer 15

Translocations, deletions, inversions of chromosomes

Question 16

Alterations that make changes in individual nucleotides (within gene level changes) more likely

Answer 16

micro instablilty

Question 17

examples of micro instability

Answer 17

• Increased point mutations
• small deletions
• insertions

Question 18

Mechanisms of macro level instability

Answer 18

Mutations in genes involved in centrosome and telomere stability, loss of cell cycle checkpoints, sister chromatid cohesion and chromosome segregation, centrosome duplication, double strand break repair (hypomethylated DNA more unstable)

Question 19

t(14;18) = a chromosome change that is diagnostic of what?

Answer 19

follicular lymphoma

Question 20

t(X,18) = a chromosome change that is diagnostic of what?

Answer 20

synovial sarcoma

Question 21

Translocations

Answer 21

Fuse new and interesting oncogenes (Bcr-abl)!

Question 22

Deletions

Answer 22

Wipe out that annoying tumor suppressor!

Question 23

Inversions

Answer 23

Wrong gene in the wrong place? Two wrongs make the right way to tumor!

Question 24

Mechanism of micro level instability: point mutations and deletions are a very common way to remove what cell cycle tumor suppressor?

Answer 24

p53

Question 25

The template for single nucleotide repairs is identified in part by the methylation status. Is this a macro or micro level instability mechanism?

Answer 25

micro

Question 26

HEREDITARY NONPOLYPOSIS COLON CANCER (HNPCC) SYNDROME

Answer 26

MISMATCH REPAIR (MMR) genes:  Detect/correct base-pair error  
Note: micro level instability

Question 27

Sporadic colon cancer

Answer 27

Somatic loss (NOT hereditary) of MMR genes or the APC gene (same gene as familial adenomatous polyposis syndrome)
Note: micro level instability

Question 28

XERODERMA PIGMENTOSUM

Note: micro level instability

Answer 28

• DNA repair defect in nucleotide excision repair
• UV radiation cross-links pyrimidine residues and cannot be repaired
• Increased skin cancers, especially after exposure to sun

Question 29

Full thickness?

Answer 29

Basal layer much thicker (extends all the way to lumen but doesn’t invade)