Exam 2 - lecture 11 on cancer

Question 1

What is the rate breast?

Answer 1

age <39 = 1/229
age 40-59 = 1/24
birth - death = 1/8

Question 2

What is the rate of prostate cancer?

Answer 2

age <39 = 10,000
age 40-59 = 1/48
birth - death = 1/6

Question 3

What are the exception of a cancers not due to old age?

Answer 3

cancer due to inherited mutations, Or due to exposure to high doses of mutagens, Plus certain leukemias (childhood leukemias).

Question 4

What are the rate of molecular event of leukemia?

Answer 4

chronic - 2 to 3

acute - 3 to 4

Question 5

What are the rate of molecular event of carcinoma?

Answer 5

in situ - 3 to 4

metastatic - 5 to 12

Question 6

What are the steps in genome change?

Answer 6

point mutations (missens, nonsense, insertions and deletions)
chromosome rearrangements (deletions, insertions, translocation ad inversions)
changes in methylation pattern
regulatory changes in gene expression

Question 7

What is HNPCC?

Answer 7

HNPCC (hereditary non-poliposis colon cancer): inherited defect in mismatch repair enzyme, so patients accumulate a very high rate of genetic mutations

Question 8

DESCRIBE the evolution of colon cancer

Answer 8

normal epithelium to early adenoma to intermediate adenoma to late adenoma t carcinoma

Question 9

WHAT Are the genes involved in colon cancer?

Answer 9

APC, SMAD4

Question 10

What is astrocytoma (glioma)

Answer 10

cancer of the brain

Question 11

oncogenes?

Answer 11

Dominantly inherited (one defective allele can predispose the cell to tumor formation)

Question 12

What do oncogenes do?

Answer 12

accelerators of cell division

STOP for Apoptosis

Question 13

tumor supressors

Answer 13

– Recessive (Mutation in one allele predispose human to cancer, but do not cause it)

Question 14

what do tumor suppressor genes do?

Answer 14

inhibitors of cell division

HELP for apoptosis

Question 15

Types of Oncogenes

Answer 15

Growth factors: TGFa, EGF
Growth factor receptors: EGFR –> breast cancer
Signaling mediators: ras (colon cancer), src, AKT
Transcription factors: myc –> lymphoma
Cell cycle components: Cyclin D1

Question 16

How to activate oncogene

Answer 16

1. hyperactive protein made in normal amounts
2. normal protein greatly overproduced
3. nearby regulatory DNA Sequence causes normal protein to be overproduced
4. fusion to actively transcribed gene greatly overproduces fusion proteins, or fusion protein is hyperactive

Question 17

What happens if tumor suppressor genes are mutated?

Answer 17

If one copy is gone/mutated, second normal allele will function.
If both copies are gone/mutated, cancer can progress (two hit hypothesis).
Replace a single normal copy and cells return to normal (cell fusion assay).

Question 18

What happens if tumor is not in the retinal cells?

Answer 18

if the second mutation arises in the connective tissue, osteosarcoma will occur

Question 19

What is the function of Rb1 gene?

Answer 19

inhibitory of a gene regulatory protien

Question 20

What are the ways of changing the status of oncogenes?

Answer 20

activating point mutations
translocation under strong promoter
amplification
overexpression

Question 21

What are the ways of changing the status of tumor suppressors?

Answer 21

inactivating point mutations
promoter methylation
gross chromosomal deletions
underexpression

Question 22

What statement describes tumors?

Answer 22

they are between oligoclonal and heterogeneous

Question 23

How does tumor react?

Answer 23

Tumor reacts via expanding of pre-existing population of resistant cells, or by rapid divisions with producing of multiple clones. 99% of them non viable, but 1% is enough to win a game

Question 24

How can metastasis occur?

Answer 24

When we push tumor to survive by producing a diverse population of cells We also push tumor to produce a cells with ability to metastasize

Question 25

How does liver metastasis occur?

Answer 25

from colorectal and gastric carcinoma

Question 26

Sequence of metastatic events

Answer 26

1. Genesis of new vasculature (angiogenesis)
2. Detachment of tumor cell from other cells; promoted by matrix degradation enzyme (MMP) and inhibited by protease and cadherins, integrins
3. Invasion (entry to vessel)
   Evasion of natural host defences
4. Arrest in small vessels
5. Attachment to vessel walls
6. Extravasation
7. Establishment of a new growing colony