CANCER GENETICS Flashcards
what are the influential factors upon cell mass?
proliferation, differentiation, cell contacts, extracellular matrix, blood supply, cell death, immune attack cancer cells
what does the control of normal cell growth require?
Requires growth factors to signal the cell to enter the cell cycle
how does the cell cycle ensure cell growth?
has internal check points that make sure DNA replication and mitosis are going ahead without errors
what happens if errors are detected at check points?
the cell cycle is stopped, & the damage/error is repaired
How do cancer cells arise?
Cell growth is usually a highly regulated process
When derailed, new cells are produced in an uncontrolled manner
what are the cell masses called?
tumours (cancerous) or neoplasms (new growth)
what is transformation?
The process of changes within a cell that lead to a neoplasm
what are benign neoplasms?
restricted to one ‘clump’ of cells – not cancerous – does not spread
what are metastatic neoplasms?
rare – primary cancer is not found - spreads
what are Familial cancers?
Inherited in families – high penetrance genes
what are Sporadic cancers?
Acquired in one’s life-time - population – combination of low penetrance genes
what are the causes of genetic damage that lead to cancer?
Cancer cells are clonal
Some chromosomal aberrations are associated with cancer
Exposure to chemicals that damage DNA increases the incidence of cancer
Infection with an oncovirus can lead to cancer
what is carcinogenesis?
the process of inducing cancer
how do cells get properties of cancer?
A population of cells acquire a series of genomic mutations
These mutations give the cells the hallmarks of cancer
what 2 sorts of genes do the hallmarks of cancer arise in?
Oncogenes
Tumour-suppressor genes
what are the different types of small scale mutation?
point
insertion
deletion
what are point mutation?
silent, missense, nonsense
what are the different types of large-scale mutations?
amplification, deletion, translocation, inversion, loss of heterozygosity
what are oncogenes?
only 1 genetic change in proto-oncogene
what are oncogenes dominant to?
Dominant to WT (GAIN of function Constitutive, excessive or inappropriate activity
what do oncogenes stimulate?
cell growth in response to growth factors
what are tumour suppressors?
2 genetic/epigenetic changes (both alleles)
what are tumour suppressors recessive to?
Recessive function to WT (LOSS of function)
what do tumour suppressors repress?
Repress aberrant cell growth/entry into cell cycle
what are Proto-oncogenes?
genes which encode for components of cell signalling pathways which promote cell growth and division
what happens when Proto-oncogenes become mutated?
they become oncogenes
what do oncogenes do?
`drive’ the cell to divide (hallmark 1)
what do oncogenes trigger?
Oncogenes trigger cell transformation
what are viral oncogenes?
essentially copies of a group of genes found in humans (porto-oncogenes)
what do Proto-oncogenes control?
control key processes in cell growth
what cell growth processes do Proto-oncogenes control?
growth factors, transcription factors, cyclins
how do Proto-oncogenes become activated oncogenes?
via gain of function events
what are gain of function events?
Activation by amplification, mutation, chromosomal rearrangement
give examples of oncogenes
her 2
ras
VEGF
what is the normal function of tumour-suppressor genes?
to inhibit cell proliferation and in some cases, trigger apoptosis
where do tumour-suppressor genes work?
at cell cycle check points
when do tumour suppressor genes stop the cell cycle?
If DNA damage has occurred, or mitosis has gone wrong
what happens once the cell cycle has been stopped?
cell `rests’ and repair is made to DNA or chromosomes
what happens if the cell can’t be repaired?
cell undergoes apoptosis
what do tumour suppressors prevent?
prevent inappropriate entry into cell cycle
what do tumour suppressors promote?
cell death of cancer cells by apoptosis
what do tumour suppressors maintain?
genome stability
what do tumour suppressors control?
the micro-environment around the cells
what are tumour suppressors classified as?
Gatekeeper genes
Caretaker genes
Landscaper genes
what do Gatekeeper genes do?
regulate cell division or growth
what do Caretaker genes do?
DNA repair or the DNA damage response
what do Landscaper genes do?
modulate the micro-environment in which tumour cells grow
are mutations in tumour suppressor genes dominant or recessive?
generally recessive
why are tumour suppressor genes recessive?
both alleles must be mutated (inactive) in order for the gene to stop functioning
give examples of tumour-suppressor genes
Rb retinoblastoma gene
p53 (TP53)
BCRA1 and BRCA2
why do viruses cause cancer?
they enhance proliferation and predispose cells to cancer, but are NOT sufficient to induce complete transformation
what is the relationship between cancer risk and age?
as age increases the number of cancer cases increases
what is the multi-stage model (‘Vogelgram’)?
external growth signals anti-growth signals apoptosis Immortality angiogenesis metastatic
