Clinical Cancer Genetics Flashcards
(40 cards)
What are polymorphisms
Changes in the DNA sequence that occur commonly in the population
What are germ line mutations
Different from polymorphisms and are rare inherited mutations that increase the risk of cancer significantly
How does genetic and environmental factors affect cancer risk
Different for different cancers
Lung cancer is very environmental
Retinoblastoma is mostly inherited
Give examples of inherited cancers
- Retinoblastoma
- Multiple endocrine tumours
- Breast cancer
- Colon cancer
How many mutations are usually required to form a human tumour cell
Evidence suggest at least 4 pathways must be mutated and that there are 3-6 rate limiting steps in the development of most cancers
What types of cancer gene are there
Oncogenes
Tumour suppressor gene
How do onco and tumour suppressor genes associated with cancer
Oncogene - gain of function or increased function associated with cancer
Tumour Suppressor gene - Loss of function or reduced function associated with cancer
What is a proton-oncogene
A normal gene that can become an oncogene due to mutations or increased expression
What proteins do proton-oncogenes code for
Proteins that help to regulate cell growth and differentiation
What processes are proton-oncogenes often involved in
Signal transduction
Mitogenic signals
What is oncogene activation
This is the conversion of a proton-oncogene to an oncogene
What is the restriction point of the cell cycle
This is the point near the end of the G1 phase of the cell cycle where beyond this point the cells will absolutely complete the cell cycle
What do Kinases do
These add phosphate to amino acids like serine (threonine kinases) or tyrosine (tyrosine kinases)
What do phosphatases do
Removes phosphate from amino acids
What do cyclins and cyclin dependent kinases (CDKs) do
These form complexes and the cyclins are regulatory and activate the CDKs
What is a major target of the cyclins
The retinoblastoma tumour suppressor gene that it phosphorylates at multiple points throughout the cell cycle
How do growth factors work
- Growth factors bind to receptors
- G-protein switch
- Kinase cascade
- Activates transcription factors
- Changes in gene expression
- Cells instructed to synthesis DNA
How do Epidermal growth factors work
- Binds to EGF receptor
- “Ras” g protein is activated
- Activates series of kinases called Raf/MEK/ERK kinases - part of the mitogen activated protein kinase complex
- ERK kinase activates transcription factors AP1 (fos/jun proteins)
- Cyclin D1 transcribed
- Cells instructed to synthesis DNA
How does the MYC proton-oncogene contribute to cancer
- Starts when a chromosomal translocation moves an enhancer sequence within the vicinity of the MYC gene
- The MYC gene codes for widely used transcription factors
- When the enhancer sequence is wrongly placed, these transcription factors are produced at much higher rates
How does the philadephia chromosome associate with choleric myelogenous leukaemia
The BCR (breakpoint cluster region) is moved next to a kinase called ABL
This chromosome is caused is caused by the translocation of pieces from chromosomes 9 and 22
BCR-ABL codes for a receptor tyrosine kinase that is constitutively active leading to uncontrolled cell proliferation
What proton-oncogenes are activated by increased gene copy number
- ERB1 - epidermal growth factor receptor
- CCND1 - cyclin D1
- MYC
Name a few tumour suppressors genes and what cancers they are associated with then the fail
- RB1 - retinoblastoma
- APC - colon cancer
- TP53 - Breast cancer
- BRCA1 and BRCA2 - Breast and Ovarian cancer
- MSH1 - colon cancer
Explain the two-hit hypothesis
If you inherited a mutated tumour suppressor gene then you were more likely to get the cancer as you might only need one more mutation for the tumour cells to be formed
What are the 2 types of tumour suppressor genes
Gatekeeper
Caretaker
