Tumour Precursors, Carcinogenesis And Genetic Changes Flashcards
(22 cards)
Evidence of precursors of invasion and metastasis in organs
Architecture of epithelium changes
Changes in cytological morphology of cells
intra-epithelial neoplasms
Pre-invasive stages in squamous epithelium
Normal -> low grade CIN -> high grade CIN -> cancer
Cytological features of high-grade cervical intra-epithelial neoplasm
Abnormal nuclei, abnormal mitosis, loss of nuclear polarity, loss of differentiation
Carcinogens
Agents which induce cancer in man or animals
Carcinogenesis
process of cancer induction
Types of carcinogen
Biological -> bacteria, viruses, parasites
Chemical -> natural synthetic
Physical -> UV or ionising radiation
How to study mechanisms of carcinogens and cancer progession
Molecular genetic analysis of cancers and their precursor legions
Animal models
In vitro carcinogenesis and immortalisation
Inherited cancers in humans - susceptibility precursors
Dose response
A linear relationship between the amount of carcinogen delivered in a single dose and the number of tumours which develop
Latent period
Time lag between the administration of a carcinogen and appearance of macroscopic tumours
Higher dose=shorter lag time
Lower dose= extended lag time
Threshold dose
The dose below which no tumours will form
Stages in carcinogenesis
Initiation -> promotion -> progression
Initiation
Alteration of normal cell into potentially cancerous cell -> caused by carcinogens acting as mutagens to cause irreversible mutations
Promotion
A process which permits clonal amplification of the initiated cell
Promoters do not act as mutagens -> they only induce proliferation
Progression
Acquisition of further mutations within the neoplasticism clone drive progression to a malignant neoplasm
Replicative sensescence
Primary cells undergo a defined number of cell divisions -> after this the cells enter cell cycle arrest and are held in G0 -> eventually dying by apoptosis
Hayflick number
The defined number of cell divisions a primary cell will undergo - approx 50-70
Telomeres
Repetitive sequences (TTAGGG) at the end of chromosomes -> which form loops to protect the chromosome end from eroding away during replication
Telomerase
Enzyme found in stem cells which maintains telomere length
Retinoblastoma
Both inherited (1 mutation pre-zygotic, 1 mutation post zygotic) and sporadic (both mutation occur post zygotic)
Syndromes in which heterozygous express the tumour phenotypes
The affected individual has genotype regular/mutant
- > autosomal dominant inheritance
- > inherit 1st mutation -> acquire 2nd mutation -> resulting genotype favours mutant
Syndromes in which homozygous have increased risk of cancer
Affected individual has genotype mutant/mutant
Homozygous for mutant gene
Inheriting 2 mutant alleles - one from each parent
What do studies of inherited cancer tell us
Cancer is a multi stage process
Maintaining error free DNA is crucial
Control restricting cellular lifespan must overcome for tumour progression
More than one mutation nis necessary for progression
Cancer is a genetic disease -> the initiating event is a somatic mutation in a single cell
