Cancer Genomes Flashcards
State a cause of cancer.
Genetic. Epigenetic mutations. Environmentally induced cancer.
How does cancer develop?
Clonal expansion.
State a feature of constitutional mutations.
Chromosomal imbalance. Single gene disorder - tumour suppressors, oncogenes. Imprinting abnormality.
State a feature of somatic mutations.
Cannot be inherited - occur in non-germline tissues.
State a feature of germ-line mutations.
Can be inherited - present in egg or sperm.
State a difference between driver mutation and passenger mutation.
Driver mutation - implicated in oncogenesis and have growth advantage. Passenger mutation - not been selected for, not conferred a clonal growth advantage (not contribute to cancer).
Give 1 example of a oncogene.
Her2-neu - breast. Ras. Myc. Src. Htert. Kras - colorectal. BRAF - melanoma.
Give 1 example of a tumour suppressor gene.
p53. Rb. APC. BRCA1. BRCA2.
Give an example of a DNA repair gene.
BRCA1. BRCA2.
State a cause of oncogene activation.
Chromosomal translocation. Gene amplification. Intragenic mutation.
How do tumour suppressor gene mutations contribute to cancer development?
Mutations inactivate inhibitory functions.
What is Knudson’s two-hit hypothesis?
Non-hereditary individual - requires a 2 hit ‘event’ (mutate both chromosomes) for a tumour. Hereditary individual - 1 hit event for a tumour.
State one way a hereditary mutation differ to a non-hereditary mutation?
Individuals with genetic mutation - more likely to develop tumour, more likely to develop tumour at a younger age.
What is a retinoblastoma?
Cancer in retina affecting young children.
What is a phaeochromocytoma?
Tumour of the adrenal gland - increases adrenaline (hormone controlling the heart rate/metabolism/BP).
What is lynch syndrome?
Hereditary non-polyposis colorectal cancer - associated with predisposition to different cancers e.g. ovarian cancer, stomach, breast, liver, kidney.
What is meant by medullary thyroid cancer?
Originates from parafollicular cells which produce calcitonin.
State 3 hallmarks of cancer.
Sustaining proliferative signalling. Evading growth suppressors. Activating invasion and metastasis. Enabling replicative immortality. Resisting cell death. Avoiding immune destruction. Tumour-promoting inflammation. Genome instability and mutation. Deregulating cellular energetics.
State a platinum based chemotherapy used to treat breast cancer.
Carboplatin - ensures DNA-cross links (DNA repair), prevent broken, damaged DNA from accumulating to cause cell death.
State an example of a PARP inhibitor.
Olaparib (in ovarian cancer) - ensures single-strand DNA breaks which are converted to double stranded DNA. This can be lethal for BRCA-deficient cells.
State a characteristic of Lynch syndrome.
Microsatellites (STRs) - have PD-L1 receptor which deactivates T cells to produce an immunosuppressive environment.
What does pembrolizumab do?
Ensures PD1-inhibition - create an immunosuppressive environment.
What does EGFR stand for, and what is its role in lung cancer?
Epidermal Growth Factor Receptor. Over expressed in non-small cell lung cancer - acts as an oncogene to promote cancer.
State a tyrosine kinase inhibitor.
Gefitinib. Erlotinib.
State the function fo a tyrosine kinase inhibitor.
Blocks the pathway - prevents lung cancer.
What is the difference between somatic and constitutional mutations?
Somatic - present in the tumour only. Constitutional - present in tumour and all other cells in the body.
