031 Molecular basis of cancer

Question 1

Which oncogene is found in bladder carcinoma, and which nucleotide mutation does this occur?

Answer 1

H-Ras oncogene

Occurs from a G–> T transversion

Question 2

What oncogene amplification determines neuroblastoma prognosis?

Answer 2

N-Myc

Question 3

What does the fusion protein BCR-Abl result in?

Answer 3

tyrosine kinase activation driving cell division and inhibiting DNA repair by production of IL3

Question 4

What is the most powerful protoncogene?

Answer 4

C-Myc

Question 5

What does C-Myc stimulate, and how does it act as a proto-oncogene?

Answer 5

Stimulates both promotion and apoptosis. In the presence of survival factors, apoptosis signals are suppressed causing proliferation. When cell is too big, this migrates away and will result in the default apoptosis. If the apoptopic factor is mutated, causes cancer.

Question 6

What is the difference between hereditary and sporadic retinoblastoma?

Answer 6

Heriditary: bilateral and removal does not prevent cancer in future
Sporadic: unilateral and removes the cancer completely.

Question 7

What is knudsons 2 hit hypothesis?

Answer 7

Raate of appearance of familial tumors consistent with single random event because 1st mutation event already inherited. Sporadic tumors behaved as if 2 random events were required.

However, these mechanisms are too rare.

Question 8

What will most retinoblastoma tumour cells show on genetic analysis, disproving the knudson 2 hit hypothesis?

Answer 8

LOH at Rb locus in tumor cells and nearby genetic markers on chromosome 13. Only small minority will have 2 distinct mutatnt alleles of Rb.

Question 9

Name a G1 checkpoint protein

Answer 9

pRB

Question 10

How does pRB control cell cycle progression

Answer 10

Checkpoint at G1 stage, preventing excessive cell proliferation and inhibiting cell cycle progression. It is phosphorylated to become inactive to allow cell cycle progression. Mutations in this causes inappropriate growth and genomic instability.

Question 11

What does P53 do?

Answer 11

Freeze at G1/S phase, activating DNA repair, and if this doesnt work then initiating apoptosis?

Question 12

How are histones lost causing unwrapping of chromatin in epigenetic changes for cancer?

Answer 12

Hypomethalation of histones cause unwrapping and increased expression of proto-oncogenes.

Question 13

How does dysregulation of microrna cause tumor formation?

Answer 13

microRNA often inhibits the gene expression in normal cells. Chromosome translocation might free mRNA from inhibition by mRNA. Used as biomarker for prognosis as well as remission and relapse.