13.4 Cancer Flashcards
What are somatic mutations?
- Acquired
- Present in only some cells
What structure is somatic tumour genetic testing conducted on? Why is this testing conducted?
- Tumour tissue
- Diagnostic/treatment purposes
List some hallmarks of cancer
- Angiogenesis
- Avoiding immune destruction
- Invading surrounding tissues
- Replicative immortality
What percentage of cancers are acquired over a person’s lifetime
95%
What is an adenoma?
Benign tumour
What is a carcinoma?
Cancerous tumour
Does activation or inactivation of tumour suppressor genes increase cancer risk? What is this known as?
Inactivation (like the brakes on a car)
“Loss of function”
Does activation or inactivation of proto-oncogenes decrease cancer risk? What is this termed?
Activation (PROTOtype -> dodgy and doesn’t work as designed)
“Gain of function”
What are the two categories of tumour suppressor genes?
- Gate-Keeper Genes
- Care Taker Genes
What are Gate Keeper Genes Responsible for?
- Cell cycle regulators
- Checkpoint control
- Apoptosis-related
(gatekeep growth)
What are care taker genes responsible for?
- DNA repair
- Cellular maintenance
(take care of genetic stability)
Which gene encodes the p53 protein?
TP53
Describe the action of the p53 protein in response to DNA damage
- Detects DNA damage
- Arrests cell cycle
- If repairable: repair
else: apoptosis
Describe driver mutations in cancer formation. What do they do, and what are they targets for?
- Directly responsible for cancer development
- Allow growth/replication, assist in apoptosis resistance etc.
- Potential therapy targets
Describe passenger mutations in cancer development
- Not responsible for cancer formation
- BUT… not random; provide “genetic” scars that could indicate how the cancer came about
What is tumour mutational burden?
The frequency of somatic mutations found in conjunction with a certain type of cancer
What are genetic mutational signatures?
Characteristic combinations of mutations, often corresponding to types of cancer
What can be the cause of “silent” cancers?
- Single oncogenic driver mutation
- Fusion driven cancers
- Chromosomal rearrangement driven cancer
- Epigenetic mutaions
Can somatic epigenetic mutations influence someone while they are in utero?
Yes; like in the Dutch Hunger Winter
What is the utility of germline genetic testing?
Risk determination
Do one or both copies of a tumour suppressor gene need to be lost in order for loss of function to occur?
Both copies (homozygous)
Do one or both copies of a proto-oncogene need to be activated in order for gain of function to occur?
Only one copy (heterozygous)
Describe Knudon’s two-hit hypothesis
- Most non-hereditary mutations require both copies of a tumour suppressor gene to become mutated
- In the case of germline mutations, only one mutation is required to cause an effect, leading to predisposition
Why can’t we directly extrapolate genotype to phenotype?
Because other environmental and genetic factors are present that affect the expression of genes
Describe autosomal dominant inheritance
- Model of inheritance where only one copy of a mutated allele is required to pass on a condition/susceptibility to a child
- If one parent has one mutated allele, child has 50% chance of having it too
What percentage of cancer predisposition arises from autosomal dominance?
1%
Do autosomal dominant cancer inheritance patternss often produce non-cancer phenotypic features?
Not usually
What is meant by “variable expressivity” in terms of autosomal dominant cancer inheritance?
Types of cancer in individuals with the same predisposition may vary
What is Li-Fraumeni Syndrome?
Germline heterozygous pathogenic variant in TP53
What does Li-Fraumeni predispose a person to?
- Breast cancer
- Brain cancer
- Gastric cancer
What is autosomal recessive inheritance?
Both copies of a gene must be mutated in order for offspring to receive a condition/predisposition
Do autosomal dominant/recessive inheritance mostly cause childhood/adulthood cancer?
Dominant: adulthood
Recessive: childhood
Which of autosomal dominant/recessive inheritance typically cause non-cancer phenotypic features?
Dominant: Don’t
Recessive: Do
Which genetic pathways are most commonly affected by autosomal recessive inheritance?
DNA pathway genes -> chromosomal instability
In which germline-inherited situation is increased risk of cancer more mutation-specific: proto-oncogene activation or tumour suppressing gene deactivation?
Proto-oncogene activation (heterozygous). Very dependent on the specific mutation that is inherited through germline cells in proto-oncogenes.
