Genetics of Oncogenes

Question 1

cancer

Answer 1

Manifestation of mutations

usually of somatic origin

threshold model does not apply for cancer

Question 2

Tumor progression

Answer 2

Normal->Hyperplatic(hyperplasia)–>Dysplastic(phenotypic differences)–> neoplasia(abnormal diffision, tumor growth)–> Metastatic

Question 3

What does tumor progression result from?

Answer 3

Waves of mutation followed by clonal expansion

Question 4

What alterations in malignant transformation lead to Increases survival and growth?

Answer 4

Self-sufficiency in growth signals

Insensitivity to growth-inhibitory signals

evasion of apoptosis

escape from immune attack

limitless replicative potential

Question 5

What alterations in malignant transformation lead to Metastasis?

Answer 5

loss of contact inhibition of growth

loss of cell-cell adhesion

ability to invade other tissue

Question 6

What alteration in malignant transformation lead to increased mutation rate

Answer 6

breakdown in DNA repair and genomic stability

Question 7

What alteration in malignant transformation lead to cancer energy supply?

Answer 7

Sustained angiogenesis

Question 8

Oncogenes

Answer 8

Normally stimulate growth

Question 9

Tumor suppressor

Answer 9

inhibit growth

Question 10

DNA Repair

Answer 10

normally limit mutations

Question 11

Proto-oncogenes

Answer 11

Produce proteins which promote cell growth or prevent apoptosis

Mutation and or over/mis expression causing cell growth

Usually gain of function mutation resulting in cancer

mutation in ONE copy sufficient to cause cancer

Question 12

Tumor suppressor genes

Answer 12

Produce proteins that inhibit the cell cycle preventing cell proliferation

Usually a Loss of Function mutation resulting in cancer

mutations in TWO copies required to cause cancer

Question 13

Mutator Genes

Answer 13

Mutations in DNA repair genes

Question 14

what is the difference between proto-oncogenes and oncogenes?

Answer 14

Proto-oncogenes are normal version of genes that can contribute to cancer when mutationally activated or inappropriately expressed.

Oncogenes are the mutant versions of the genes

Question 15

What do proto-oncogenes produce

Answer 15

proteins that regulate cell proliferation

Question 16

Burkitt lymphoma is caused by what

Answer 16

activation of myc

Question 17

Chronic Myeloid leukemia is caused by what

Answer 17

activation of abl

Question 18

Burkitt lymphoma

Answer 18

Blood malignancy

myc oncogene is fused to immunoglobulin locus

Question 19

Myc gene and role in Burkitt Lymphoma

Answer 19

• Myc is a transcription factor important for G1/S transition
• Level og oncogene expression is increased as myc is under the regulation of IgH promoter
  
  • leads to increased myc production
  • B-lymphocytes undergo rapid cell divisions resulting in malignant phenotype

Question 20

what is this an image of?

Answer 20

BCR-Able translocation in chronic myeloid leukemia

Question 21

what is this an image of?

Answer 21

The philadelphia chromosome translocation t(9;22)(q34;q11)

Question 22

Imaniteb and anticancer application

Answer 22

Is a powerful tyrosine kinase inhibitor- for Bcr-abl

Effective against the bcr-abl fusion protein which is stuck in its activated form

Binds to the active site of the fusion protein, bcr-able, and prevents its activity.

Question 23

What is this an image of?

Answer 23

Pharmaceutical application of Imaniteb

Question 24

Activation of Ras proto-oncogene

Answer 24

A GTPase involved in the major cell proliferative pathway(MAPKinase)

• activated by binding to GTP
  
  • Initiates a phosphorylation cascade that activates cellular proliferation
    
    • quickly inactivated by intrinsic GTPase activity ( GTP->GDP)
    • Constant stimulation is needed to grow

Question 25

Oncogene activation of Ras

Answer 25

• Ras GTP activates the growth pathway while Ras GDP is the inactive form where no growth occurs
  
  • Many mutations inhibit the GTPase activity that will allow Ras to stay active, even in the absence of a growth factor
    
    • Ex) single point mutation at Gly12 or Gln61

Question 26

Double minutes

Answer 26

Extrachromosomal fragments of DNA containing an amplified oncogene

Ex) EGFR is often amplified as double minute chromosome(seen in red in the image) in advanced gliomas which can be visualized by FISH Probes

Question 27

What is Her-2

Answer 27

Human Epidermal Growth Factor Receptor 2

Question 28

HER2+ tumors and Herceptin relationship

Answer 28

HER2+ tumors have increased HER2 receptors on the tumor

Trastuzumab is a Herceptin drug that binds to those receptors so that growth factors can not bind

results in decreased tumor cell proliferation

Only effective for HER2+