Introduction Flashcards
recommended reading molecular biology of cell cancer biology human molecular genetics
Definition
heterogeneous group of diseases where single cells acquire ability to proliferate abnormally - accumulation of progeny
tumours acquired ability to invade surrounding tissues
Carcinoma
epithelial
Sarcoma
mesoderm
leukaemia/lymphoma
blood cell precursor
benign
localised, non-invasive
malignant
invasion and metastasis
benign —> malignant
progression
Angiogenesis
formation of new blood vessels
Rate limiting step in growth
every cancer cell needs to be within 1mm of blood supply
Metastasis
leave initial site and transit to distant sites via blood/lymph and body cavities
Malignant melanoma can travel to
brain and liver
intravasation
into vessel
Mutation
stably inherited change in genetic material
Evidence for genetic basis
inheritance
sporadic mutations are transforming
chromosomal changes common - particular to cancer
agents damage DNA —> increase cancer risk
diseases from DNA defects —> increase cancer
infection certain viruses —> development cancer
Tobacco smoke responsible for
20-30% cancers
Types mutation
Chromosome number change - ploidy change
translocations
amplifications
interstitial gains and losses
small deletions/insertions and single base pair muatations
exogenous sequences - viruses in cervical cancer HPV, burkitts lymphoma EBV, hepatocellular carcinoma hepatitis, kaposi’s sarcoma HIV
epigenetic mechanisms - promoter hypermethylation, inherited as cells divide
Cancer is rare at cell level due to
DNA repair mechanisms (highly evolved)
apoptotic mechanisms
mutations usually not affect growth
most DNA not code protein
rapidly dividing cells (skin) lost so not matter if mutations
many cells lose potential to divide after differentiation
single mutation not escape defences
Mutation increase growth, division, survivial
expand population for subsequent mutations (bigger target)
mutation alter genomic stability
increase mutation rate and susceptibility to further mutations, 2nd mutation not repaired
oncogenes normal role (proto-oncogene)
promote proliferation, growth, invasion
oncogene gain of function
1 allele - excessive/inappropriate activity
Tumour suppressor normal
inhibit events leading to cancer, inhibit and slow growth
tumour suppressor loss of function
2 alleles - inactivation and cancer development
Gatekeeper
control proliferation
caretaker
control rate of mutation
adenoma
benign tumour
Feature of cancer development
order mutations important
Hanahan and Weinberg principles
Independence of external growth signals insensitivity to external anti-growth signals avoid apoptosis indefinite replication angiogenesis metastatsis/invasion
