Genes that Predispose to Cancer

Question 1

What does Gleevec target?

Answer 1

BCR-ABL in chronic myeloid leukaemia

Question 2

In which type of cancer is Ras commonly mutated?

Answer 2

Colon cancer

Question 3

What treatment is available to chronic myeloid leukaemia?

Answer 3

Imatinib (Gleevec)

Question 3

Which Cylin initiates the cell cycle?

Answer 3

CylinD-CDK4

Question 4

Why are B cells particularly prone to developing into neoplasms?

Answer 4

The antibody diversification process including class switching and somatic hypermutation cause increased mutations in non-Ig genes

Question 5

How does the Bcr-Abl aberration arise?

Answer 5

Due to a philadelphia chromosome between 9 and 22

Question 6

Which lymphoid cell makes up the majority of the lymphoid neoplasms?

Answer 6

B-cells

Question 6

What type of protein is ABL?

Answer 6

A kinase

Question 7

Changes in which factors in CLL are associated with poor prognosis?

Answer 7

ZAP-70

p53

Question 9

What are the six classical hallmarks of cancer?

Answer 9

Evasion of apoptosis

Autonomous replication

Cell immortality

Angiogenesis

Evading growth inhibitory signals

Activating invasion and metastasis

Question 10

What do CylinD’s do?

Answer 10

Regulate the cell cycle

Question 10

Why is Gleevec so well tolerated?

Answer 10

It only target 3 kinases (out of 90)

Question 11

What is the major mechanism of CLL formation?

Answer 11

Loss of miRNA 15a and 16-1 regulation of Bcl-2 > loss of apoptosis

Subsequent changes in ZAP-70 and p53

Question 12

Which 2 proteins mediate the miRNA silencing of mRNA?

Answer 12

Dicer

RISC

Question 14

What does Bcl-2 control the cell?

Answer 14

Retention of cyt c proteins in the mitochondria to promote cell survival

Question 15

What mutation leads to the development of chronic myeloid leukaemia (CML)?

Answer 15

Philadelphia chromosome: Bcr-Abl

Question 16

Why isn’t Gleevec curative?

Answer 16

Because the mutated progenitor cells do not cycle often therefore are protected from Gleevec

Question 17

What is the primary mutation that leads to the development of chronic lymphocytic leukaemia?

Answer 17

Bcl-2

Question 19

Blast crisis’ occur in which type of leukaemia?

Answer 19

CML

Question 20

How does ZAP-70 act in CLL?

Answer 20

Increase the pro-survival effect of Bcl-2

Question 21

In which pathology are smudge cells found?

Answer 21

CLL

Question 22

How does a mutated BCR-ABL protein cause neoplasmic transformation?

Answer 22

It activates proliferation, anti-apoptosis, migration and change in metabolism

Question 23

How do new CLL treatments work?

Answer 23

ABT-199 which blocks excessively high levels of Bcl-2

Question 24

What precipitates a CML blast crisis?

Answer 24

The acquisition of a further mutation, separate from bcr-abl, that increases its potential to cause damage