CA2: Clinical Cancer Genetics Flashcards
What type of mutations do all cancers have?
All cancers have somatic mutations
Changes in the DNA sequence that occur commonly in the population are termed?
Polymorphisms
Some individuals carry rare germ lie mutations, what do these do?
Increase the risk of particular cancers from between 5 and >1000 fold
Give some examples of inherited cancers? (4)
- Retinoblastoma
- Multiple Endocrine Tumours
- Breast Cancer
- Colon Cancer
How many pathways must mutate to create a human tumour cell according to experimental evidence?
Experimental evidence suggests at least four pathways must be mutated to create a human tumour cell
What can make a proto-oncogene into an oncogene? (2)
- Mutations
- Increased expression
Proteins produced by oncogenes are termed?
Oncoprotein
Proto-oncogenes code for protein that help regulate what? (2)
- Cell growth
- Differentiation
Name 2 things that proto-oncogenes are often involved in regarding signals?
- Signal transduction
- Execution of mitogenic signals
The conversion of a proto-oncogene to an oncogene is termed?
Oncogene activation
What do kinases do?
Kinases add phosphate to amino acids like serine and tyrosine
What do phosphatases do?
Phosphatases remove phosphate from amino acids.
What do cyclins and cyclin-dependent kinases form?
Complexes
Explain generally how growth factors instruct cells to synthesise DNA
- Growth factor binds to receptor
- Activation of oncogenes and cascade of events
- Transcription factor activated
- Cyclin d1 transcribed
- cdk4 forms DNA
What causes the over-expressed oncogene (MYCgene)?
Chromosome rearrangement
In what medical condition is the MYCgene implicated?
Burkitt’s Lymphoma
Explain the events causing MYCgene implication
- 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
What does the Philadelphia chromosome cause?
Chronic Myelogenous Leukemia
Explain the events leading unto the Philadelphia chromosome and what does it code for?
(What chromosomes are involved?)
(What gene is involved?)
- Translocation between chromosome 9 and 22
- Chromosome 22 now becomes the ‘Philadelphia chromosome’ which contains the BCR-ABL gene
- Bcr-Abl codes for a receptor tyrosine kinase, leading to uncontrolled cell proliferation.
What are gatekeeper tumour suppressor genes?
Gatekeeper genes that regulate tumour growth by controlling proliferation or promoting cell death
What are caretaker tumour suppressor genes?
Caretaker genes are generally DNA repair genes or genes that otherwise protect the genome from acquiring or retaining DNA damage
What is the cancer risk increase if a gatekeeper gene is inactivated? Why?
Gatekeeper gene inactivation leads to a very large increase in cancer risk >1000 fold because only one further mutation is required to initiate neoplasia.
What is the cancer risk increase if a caretaker gene is inactivated? Why?
Caretaker gene inactivation leads small increase in cancer risk 5-50 fold because up to three further mutations are required to initiate neoplasia
What and how many mutations are required for the ATM gene to generate a cancer?
What type of gene is this?
- 1 germ line mutation
- 2 somatic gatekeeper mutations
- 3 in total
- Recessive gene
What and how many mutations are required for the BRCA1 gene to generate a cancer?
What type of gene is this?
- 2 somatic gatekeeper mutations
- 2 in total
- Dominant gene
pRB gene;
Function?
Which cancers? (2)
- Control of restriction point
- Retinoblastoma
- Osteosarcoma
CDKN2A gene;
Function?
Which cancer?
- Control of restriction point
- Melanoma
TP53 gene;
Function?
Which cancers?
- Control of the cell cycle and apoptosis
- Breast cancers and several others
APC gene;
Function?
Which cancer?
- Control of the cell cycle and apoptosis and differentiation
- Colon cancer
Mutations in nucleotide excision repair genes can cause which cancers?
Skin cancers
Mutations in mismatch repair genes can cause which cancer?
Colon cancer
Mutations in BRCA1 and BRCA2 can cause which cancer?
Breast and ovarian cancer
How can viruses in rodents and chickens cause cancer? (2)
- Recruit and modify versions of proto-oncogenes and activate them
- Activate them by inserting powerful viral enhancers sequences next to them
How is cervical cancer caused?
- Caused by the human papillomavirus
- Encodes proteins E6 & E7
- These inactivate key tumour suppressor genes
(RB1 & TP53)
