Genetics Of Cancer Flashcards
How many hallmarks of cancer are there
8
What do the 8 hallmarks of cancer allow
Carcinogenesis and malignant growth
8 hallmarks of cancer
Self sufficiency in growth signals
Insensitivity to anti growth signals
Evade apoptosis
Militless reproductive potential
Sustained angiogenesis
Tissue invasion and metastasis
Deregulated cellular energetic
Avoid immune detection
Why are proteases and cytoskeletal proteins upregulated in cancer cells
To breakdown Basement membrane and allow migration
Why are mutations in cancer cells not corrected
Defective DNA repair proteins
What type of signalling is used by cancer cells to enhance cell division
Autocrine
3 main groups of genes associated with cancer
Oncogenes
Gatekeeper and caretaker genes - tumour suppressor genes
How do gatekeeper tumour suppressor genes prevent cancer
Regulate and restrict cell cycle
Induce apoptosis in mutated cells
How do caretaker tumour suppressor genes prevent cancer
Repair DNA
What is the role of proteins encoded by proto oncogenes
Control cell growth and cell division
What is produced when a proto oncogene is mutated
Oncogene
What proteins are encoded by proto oncogenes
Growth factors
Receptors
Intracellular signalling proteins
Transcription factors
Anti apoptotic proteins
Increased activity of what type of protein leads to excess cell division and uncontrolled cell growth
Kinases
Do proto oncogenes become oncogenes by a gain of function or loss of function mutation
Gain of function
Does activation of an oncogene from a proto oncogene require a single or double mutation
Single
What cell structures on cancer cells are highly active and play a role in cancer cell motility
Lamellipodia
How do tyrosine receptors facilitate activation of growth promoting signalling pathways
Growth factor binds and tyrosine receptors dimerise activating kinase activity
2 major growth signalling pathways
MAPK pathway
Pi3 kinase pathway
Role of MAPK pathway
Cel proliferation
Apoptosis regulation
Pi3 kinase pathway role
Cell growth
Proliferation
Angiogenesis
metabolism
How do kinases effect proteins
Phosphorylate
What is constitutive phosphorylation of tyrosine kinase receptors
Mutation in ATP binding site means receptor remains phosphorylated so signalling transduction cannot be switched off leading to excess growth via MAPK/Pi3
What does overexpression of HER2 lead to
Uncontrolled growth
Survival of mutated cells
Invasion of tumour cells
Migration of tumour cells
What is HER2
Receptor tyrosine kinase
How does increased expression of HER2 cause cancer
Increased number of tyrosine kinase receptors causes increased cell growth signalling
Why is HER2 more oncogene that other tyrosine kinase receptor genes
HER2 receptors don’t need growth factor to be activated
Where are HER2 receptors found
Cell surface membrane
What type of gene are BRCA1 and 2
Care taker genes
Do tumour suppressor genes undergo a loss of function or gain of function mutation to cause cancer
Loss of function
Do tumour suppressor genes need 1 or both genes to be mutated to cause cancer
Both
What happens when the cell cycle is not regulated at checkpoints
DNA damaged cells not repaired or apoptosed so continue through cell cycle causing cancer
What transcription factor is activated when DNA damage is detected at cell cycle checkpoints
P53
How does P53 prevent DNA damaged cells continuing through cell cycle
Activates P21 which inhibits cyclin dependent kinase arresting the cell cycle
Activates pro apoptotic genes
Where in the cell cycle does Inhibition of the cyclin E/CDK2 complex cause arrest
G1/S checkpoint
Where in the cell cycle does cyclin B/CDK1 complex inhibition cause cycle arrest
G2/M checkpoint
What is the most commonly mutated gene in cancer
TP53
What causes Inhibition of cyclin B/CDK1 and cyclin E/CDK2 complexes
P53
Role of pRb
Inhibits S phase gene expression to prevent cell cycle progression past G1
What type of cancer is caused by pRb mutation
Retinoblastoma
Main role of BRCA2
Regulates RAD51 function to repair DNA damage by homologous recombination
Role of BRCA1
Involved in Multiple cellular processes in response to DNA damage
What type of DNA damage are BRCA genes most important in repair of
Double strand breaks
What is caused by loss of BRCA genes
Strand breaks and aneuploidy after cell division
How do cancer cells avoid apoptosis
Upregulates anti apoptotic proteins or down regulate pro apoptotic proteins
Are BAX, BAK, and BCL2 pro or anti apoptotic
BAX and BAK - pro apoptotic
BCL2 - anti apoptotic
What type of protein is BCL2
Anti apoptotic
How do cancer cells maintain their telomeres to allow unlimited replication
Upregulate telomerase reverse transcriptase TERT to produce more telomerase
What protein is synthesised by telomerase
Telomere
What repair mechanisms fix single strand breaks, bulky adducts , nucleotide mutation/substitutions/deletions/insertions, and double strand breaks (from clinical trial workshop)
Single strand break - base excision repair
Bulky adducts- nucleotide excision repair
nucleotide mutation/substitutions/deletions/insertions - mismatch repair
Double strand breaks - homologous recombination, non homologous end joining, microhomology mediated end joining
Is homologous recombination, non homologous end joining, or microhomology mediated end joining of double strand breaks least mutagenic (from clinical trial workshop)
Homologous recombination
