Genetic mechanism of oncogenesis

Question 1

What’s the genetic mechanism of oncogenesis when there’s interstitial deletion in 5q?

Answer 1

1) Gene dosage effect caused by multiple genes contained in the 5q region (genes involved in haematopoeisis) => AML OR
2) Deletions in 5q common in MDS (not sure if tumour suppressor gene/oncogene is involved

Question 2

What is the result of 5q interstitial deletion? What disease is expressed?
*NOTE: interstitial deletion: 2 break points involved

Answer 2

AML: due to those genes involved in haematopoesis being deleted
MDS (myelodisplastic syndrome): Deletions in 5q common

Question 3

What is the result of t(9;22)? What disease is expressed?

Answer 3

commonly CML (& some cases of ALL)

Question 4

What’s the genetic mechanism of oncogenesis with t(9;22)?

Answer 4

Novel hybrid fusion gene BCR::ABL1 on der(22) => chimeric protein => dysregulates proliferation

• BCR: (22q11)
• ABL1: (9q34) > encodes for tyrosine kinase activity for cell differentiation

Question 5

What is the result of t(14;18)? What disease is expressed?

Answer 5

Commonly follicular lymphoma (& some cases of non-hodgkin’s lymphoma)

Question 6

What’s the genetic mechanism of oncogenesis with t(14;18)?

Answer 6

BCL2 w/ IGH => de-regulated expression of BCL2=> inhibit apoptosis = inc proliferation

• BCL2 (18): regulates apoptosis
• IGH (14): regulation control

Question 7

What is the result of double minutes (dmins)? What disease is expressed?

Answer 7

commonly AML (other forms of cancer)

Question 8

What’s the genetic mechanism of oncogenesis with dmins?

Answer 8

Amplification of c-myc (oncogene)

- myc: involved in transription regulation

Question 9

What is the result of pericentric inversion of 16? What disease is expressed?
*NOTE: PERIcentric: inversion in b/w centromere

Answer 9

.

Question 10

What’s the genetic mechanism of oncogenesis with a pericentric inversion of 16?

Answer 10

Novel hybrid fusion CBFbeta-MYH11 at 16q22 => chimeric fusion protein => binds to RUNX1 = inhibits its function

• MYH11 (16p13): encodes a protein - converts chemical energy to mechanical energy
• CBFbeta (16q22): transcription factor - interacts w/ RUNX1

Question 11

What is the result of t(8;21)? What disease is expressed?

Answer 11

commonly in AML of M2 sub-type

Question 12

What’s the genetic mechanism of oncogenesis with t(8;21)?

Answer 12

Novel hybrid fusion gene RUNX1-RUNX1T1 => chimeric protein=> transforming oncogenic activity

Question 13

What is the result of t(8;14)? What disease is expressed?

Answer 13

mostly in Burkitt’s lymphoma (& sometimes non-hodgkin’s lymphoma)

Question 14

What’s the genetic mechanism of oncogenesis with t(8;14)?

Answer 14

MYC w/ IGH => de-reg. expression of myc => proliferation

- myc: encodes for transcription factor