Cancer as a genetic disease

Question 1

What is the difference between somatic and germline mutations?

Answer 1

Somatic - occur in body cells, cannot be passed to offspring (90% cancers)
Germline - mutations in gametes, can be passed to offspring

Question 2

What is the difference between driver and passenger mutations?

Answer 2

Passengers - don’t contribute to overall development of cancer but have occurred during the growth of cancer
Driver - contributes to cancer development

Question 3

What mutations are associated with HNPCC (hereditary non polyposis colorectal cancer?

Answer 3

MLH1 or MSH2 (DNA repair genes)

ALSO APC mutation from familial adenomatous polyposis

Question 4

Define oncogene

Answer 4

proto-oncogenes that have been activated into overdrive
over-promote growth and proliferation of cells
cause signalling cascades and mitogenic pathway activation

Question 5

Define tumour suppressors

Answer 5

Regulate cell division, DNA damagge checkpoints, apoposis, DNA repair
Mutations cause it to lose function = faulty cell division
Most require damage to both alleles to cause a phenotypic effect

Question 6

How can chromosome rearrangements contribute to oncogenesis?

Answer 6

Fusion of 2 intragenic regions can potentially create new genes with oncogenic properties
e.g. chronic myeloid leukaemia

Question 7

How are chromosome translocations used to quantify residual disease in leukaemia?

Answer 7

RARα binds strongly to DNA
Blocks transcription and differentiation of granulocytes
ATRA(chemo drug) dissociates RARα from DNA but doesn’t kill cells
These can be monitored with RQ-PCR/FISH