Cancer in Children Flashcards
What are the most common types of cancer in:
0-14 yrs [1]
15-19 yrs [1]
0-14 yrs: leukemia
15-19 yrs: lymphomas
At what age are the following usually diagnosed before? [1]
Wilms tumour
Retinoblastoma
Neuroblastoma
Acute lymphoblastic leukaemia
Are they due to a high frequency of mutations or low frequency? [1]
before 5 yrs old
Low mutation frequency in children’s cancer
Why are children more suscepitble to cancer? [2]
Naturally undergoing rapid developmental growth, with fewer brakes on their proliferation than cells in adults.
tumour precursor cells are negotiating crucial developmental checkpoints that are susceptible to corruption, leading to incomplete or abnormal cellular maturation
What are the two main types of cancer genes? [2]
Are they dominant or recesive? [1]
ONCOGENES: dominant
TUMOUR SUPPRESSOR GENES: recessive (need double knock out)
What are oncogenes activated by? [4]
Activated by gain of function mutations:
- mutation
- chromosome translocation
- gene amplification
- retroviral insertion
What are tumour suppressor genes inactivated by? [3]
Inactivated by:
* mutations
* deletions
* DNA methylation (epigenetic)
How does Wilm tumour present? [3]
- Tumour of the kidney (aka nephroblastoma)
- Mostly children under 5
- asymptomatic abdominal mass without metastasis
- Often bilateral
Heritable cancers often have which two characteristics [2]
- organs affected / bilateral cancers [1]
- present in yound children / children under 5 [1]
Describe the molecular pathology of Wilms tumour
Which genes are affected if somatic gene alterations occur [3]
Which genes are affected if germline alterations occur? [2]
Somatic gene alterations:
* In WT1, WTX and TP53 genes
* Inactivated CTNNB1 (beta catenin gene
* Epigenetic changes at IGF2/H19 locus
Germline alterations:
* In WT1 genes
* Inactivated CTNNB1 (beta catenin gene
What is the key role of WT1 gene? [1]
Ureteric branching - has key role in the epithelial induct of the metanephric mesenchyme
WT1 is critical in the key pathways for the developing kidney!
What type of genes are WT1, WTX & TP53? [1]
WT1, WTX & TP53 are Tumour Suppressor Genes
Which type of cells does Wilms tumour arise from? [1]
Wilms tumour contains the three cell types are present in the embryonic kidney, what are they? [3]
pluripotent embryonic renal precursors
blastema, epithelia, stroma (the three cell types present in the embryonic kidney)
Why would you want to engage a family in genetic counselling if their child has bilateral kidney wilms tumour? [1]
Bilateral indicates that cancer is due to heritable mutation
Tx for Wilms tumour? [2]
Treatment: surgery, chemotherapy
Use of radiotherapy is decreasing
Explain pathophysiology of retinoblastoma
- Which gene is mutated?
- Which cells are effected?
- Overview of mechanism?
germline mutation of RB1 gene usually present in patients
Occurs in cone precursor cells
Signalling pathways promote cell survival after loss of RB1
How does Rb gene work under normal function? [2]
Explain how mutation to Rb gene causes cancer [1]
Normal:
* Keeps cells at G1 phase: stops cell cycle progession.
- When it becomes phosphorylated, releases E2F (a transcription factor) which induces G1 –> S transition
Pathology:
* Mutation causes no Rb1 hyperphosphorylation due to lack of binding to E2F
