Lecture 23 - Inherited disorders 3 Flashcards
What is the basic mechanism of cancer
‘Uncontrolled’ cellular growth can be considered a natural Darwinian process whereby a cell picks up genetic variations that confers a selective growth advantage to it and its progeny
In a multi-system organism, genetic mechanisms exist to suppress this Darwinian instinct
What are some features of cancerous cells
The ability to replicate indefinitely
The ability to evade apoptosis
What are some key examples of early drivers of some cancer
mutations that inactivate DNA repair pathways
mutations that increase the rate of cell division and therefore DNA replication
What is a Stem cell
A singe cell that can either - Replicate itself or
Differentiate into many cell types
What are oncogenes
These are genes when ‘activated’ in a certain way will drive cancerous transformation
The activation usually involves a somatically occurring ‘gain-of-function’ mutation, and this only needs to occur in one copy of the gene
Associated cancers usually occur sporadically with no family history
What are tumour suppressor genes
These usually carry out some function that suppresses tumour formation
Their biallelic inactivation via mutation contributes to tumorigenesis
Associated cancers much more commonly display a family history, but can also occur sporadically more rarely
Was are the 2 major human breast cancer genes
BRCA1 and BRCA2
If a mutant copy of the BRCA1 or BRCA2 gene is inherited, the risk of breast cancer jumps to ~60% and ~45% respectively by 70 years of age
The genes encode proteins required for efficient repair of damaged DNA
What does HR stand for
Homologous recombination
What does NHEJ stand for
Non-Homologous end Joining
What is Fanconi’s anaemia (FA)
congenital condition associated with bone marrow failure, developmental abnormalities present at birth and an increased risk of leukaemia
Biallelic mutations in any one of several genes can cause FA
It was found that biallelic mutations in BRCA2 can also cause FA
What are the outcomes from parental genotypes of Normal BRCA2 and Defective BRCA2
Breast cancer
What is the result of parental genotypes of defective BRCA2
Fanconi’s anaemia
What is Von Hippel-Lindau syndrome
characterised by fatigue, poor motor co-ordination and vision impairment
One mutated copy of the VHL gene is sufficient for the disease to manifest
Somatic inactivation of the second VHL copy leads to tumours in the vasculature that supplies various systems/organs
Slide 6 on drug working
What is the Philadelphia chromosome
Containing some of the ABL gene and BCR gene and translocated to create an altered chromosome 22 (slide 8)
How does leukaemia work
Abl can be turned on or off, leading to regulation
in leukaemia Abl is always on, leading to uncontrolled division
What is MYCN amplification
Genes that drive proliferation of early neural cells
transcription factor,
over activation of promotors, and over production of genes
Where does this MYCN occur
Neuroblastomas, very common form ofchildhood form of cancer
What are knudson’s two-hit hypothesis
Slide 13
What is the role of BRCA 1
Sense single strand of DNA after beak
Recruits BRCA2 and RAD51 to create strand invasion (slide 16)
What happens on a dodgy transcription of hypoxia
Slide 20
