Cancer in children Flashcards
How many children are affected by cancer in the UK
1/500
What % of childhood cancers are brain tumours
25
What are the effects of cancer treatment exaggerated in childhood
Chemotherapy gets incorporated into dividing cells, there are lots of dividing cells in childhood as they’re growing and developing
What is an embryological tumour
Malignancies originating in developing tissues and organ systems
What does cancer arise from
Accumulation of genetic aberrations in somatic cells
What do aberrations consist of
Mutations and chromosome defects
How do oncogenes act
By gain of function
Does one or both allele need to be activated in oncogenes
Just one
Name 4 ways in which oncogenes are activated
Mutation
Chromosome translocation
Gene amplification
Retroviral insertion
How do tumour suppresor genes acts
By loss of function
Do you need to inactivate both alleles for tumour suppressor genes to cause cancer
Yes
Describe the two hit model for tumour suppressor genes
Deletion/ mutation in somatic or inherited cells
Then a second hit
What forms can the ‘second hit’ in the 2 hit model take
Loss Loss and duplication Chromosome deletion Mutation Recombination
Another name for Wilm’s tumour
Nephroblastoma
How many children are affected by Wilm’s tumour
1/10,000
How does Wilm’s tumour usually present
Asymptomatic abdominal mass without metastasis
What is WAGR?
Wilm’s tumour
Aniridia
Genito-urinary abnormalities
Mental Retardation
Name a predisposition syndrome associated with Wilms tumour
Beckwith-Wiedeman Syndrome
What cells does Wilm’s tumour arise from?
Pluripotent embryonic renal precursors
What 3 cell types present in embryonic kidney and are found in Wilm’s tumour>
Blastema
Epithelia
Stroma
What does Wilm’s tumour resemble?
Nephrogenic mesenchyme
What somatic genes are inactivated in Wilms tumour (3)
WT1
WTX
TP53
What gene is activated in wilms tumour
CTNNB1
What germline altercations occur in Wilm’s tumour
WT1 gene
1GF2/H19 locus
What is the function of WT1
Key role in uteric branching
What happens if WT1 expression doesn’t increase as it should?
WT1 stuck in condensate stage
Kidney remains immature embryological stage
In what age do retinoblastomas usually occur
Children under 5 years
Symptoms of retinoblastoma
Leukocoria (white pupil)
Eye pain
Redness
Vision problems
In what % of cases in retinoblastoma metastatic
10-15%
What is the cellular origin of retinoblastoma
Cone precursor cells
What is the normal role of RB1 protein
Phosphorylation of RB1 releases ERF inducing transition from G1 to S in cell cycle
What happens when there is no RB1
No regulation from G1 phase to S phase
As well as RB1 loss, what other molecular changes occur in retinoblastoma
MYCN activation
MDM2 or MDM3 amplification leading to inactivation of p53
What is a neuroblastoma
Tumour of the sympathetic nervous system usually arising in the adrenal gland or sympathetic ganglia
What is the most common cancer in first year of life
Neuroblastoma
What % of neuroblastoma are metastatic
50
What is the cellular origin of neuroblastoma
Derived from sympatho-adrenal lineage of the neural crest during development
Name 2 key genes involved in development of neuroblasotoma
MYCN
ALK
What does it mean if child have >10 copies of MYCN gene
Usually a worse outcome of neuroblastoma
Where do deletions occur in neuroblastoma
1p and 11q
What targeted therapy can be used to treat neuroblastoma
Crizotinib against ALK mutation
What is the most common malignancy in children
Acute lymphoblastic leukaemia
What do ALL patients present with
Bruising or bleeding
Pallor or fatigue
Infection due to anaemia
What organs can often by infiltrated by ALL
Liver
Spleen
Lymph nodes
What cell does ALL with MLL translocation affect
Pro-B cells
CD 19
What cell does ALL with high hyperdiploidy or TEL-AML1 translocation affect
Pre-B
CD19 and CD10
Is pro-b or pre-b ALL favourable?
Pre-B
