L11 - Mutations and Cancer Flashcards
What are large scale alterations
Chromosomal rearrangements
What are small scale alterations
One or a few nucleotides altered
What are the different small scale mutations
Subsitutions or insertions/deletions
What are the different types of substituion mutations
Silent, missense, nonsense
What is a silent mutation
A substitution mutation that changes a base, but does not change amino acid sequence
What is a missense mutation
A substitution mutation that changes a base and changes ONE amino acid in the sequence
What is a nonsense mutation
A substitution mutation that changes a codon to a stop codon, so amino acid sequence comes to a premature stop
What happens if 3 nucleotides are inserted or deleted
Frame is maintained, but one amino acid missing
What is Huntington’s Disease caused by
A triplet repeat expansion - lots of extra glutamines (CAG)
What is sickle cell anaemia
An example of a missense substitution mutation
Wild-type B-globin DNA mutated becomes Mutant B-globin DNA
Val instead of Glu
What is cyclin
A protein that fluctuates throughout the cell cycle
What is cyclin dependant kinase (Cdk)
A kinase that is activated (by phosphorylation) when attatched to a cyclin
What is Maturation promoting factor (MPF)
A specific cyclin + Cdk complex - key for G2 checkpoint
What does maturation promoting factor (MPF) do?
Phosphorylates many other proteins and allows mitotic phase to commence
How does the amount of Cdk change at the G2 checkpoint
Cdk is always present / stays the same
How do the cancer-causing DNA mutations arise?
Genetic predisposition - in all cells of the body
Acquired: locally, in one cell initially
What causes tumours to form
Uncontrolled cell growth
What are proto-oncogenes
Genes that normally stimulate cell proliferation
What are tumour suppressor genes
Genes that normally keep proliferation in check
What are examples of proto-oncogenes
Ras - GTPase
Myc - a transcription factor
What are examples of tumour suppressor genes
TP53 (makes p53)
BRCA1 and BRCA2
Which tissue would you sample for DNA analysis of possible cancer-causing mutations?
Usually the tumour tissue itself
Not always blood
How does colon cancer develop
- Loss of tumor-suppressor gene APC
- Activation of Ras oncogene
- Loss of tumour-suppressor gene SMAD4
- Loss of tumour suppressor gene p53
- Additional mutations
What does benign and malignant mean?
Benign - non cancerous
Malignant - cancerous
