ACTIVATION AND DEACTIVATION OF ONCOGENES

Question 1

What is a chimeric fusion gene?

Answer 1

A fusion gene that produces a fusion protein with oncogenic properties

Example: t(9;22) BCR-ABL in chronic myeloid leukemia (CML) activates ABL’s tyrosine kinase activity permanently.

Question 2

What is the effect of transposing a gene to the control of an active promoter?

Answer 2

Inappropriate over-expression of the gene

Example: t(8;14) in Burkitt lymphoma transposes cMYC next to the Immunoglobulin heavy chain locus.

Question 3

What is the significance of the EWS/FLI1 fusion in Ewing sarcoma?

Answer 3

It represents a switch between DNA binding and activation domains of a transcription factor

This leads to the activation/deactivation of a large set of genes.

Question 4

What does DNA amplification result in with respect to proto-oncogenes?

Answer 4

An increase in copy number of a proto-oncogene

Example: HER2/Neu amplification in breast cancer.

Question 5

What is the consequence of a deletion of a chromosome region?

Answer 5

Loss of tumor suppressor genes or other critical genes

Example: RB gene on chromosome 13q, TEL gene in ALL, monosomy 5 or 7 in myeloid leukemia.

Question 6

What is the role of the RB gene?

Answer 6

It is a tumor suppressor gene located on chromosome 13q

Its deletion contributes to tumorigenesis.

Question 7

True or False: Chromosomal rearrangements can activate oncogenes.

Answer 7

True

They can lead to mechanisms such as gene fusion and amplification.

Question 8

Fill in the blank: The EWS/FLI1 fusion acts as an ________ transcription factor.

Answer 8

aberrant

This fusion alters gene expression significantly.

Question 9

What is the impact of monosomy 5 or 7 in myeloid leukemia?

Answer 9

It is associated with the loss of tumor suppressor genes

This contributes to the development of myelodysplastic syndromes (MDS).