Cancer in Children Flashcards
Name the four most common cancers to affect children under the age of 5.
Acute lymphoblastic leukaemia (ALL), WIlms’ tumour, retinoblastoma and neuroblastoma
What is the most common cancer that presents in children under the age of 5?
Acute lymphoblastic leukaemia
How may a child with acute lymphoblastic leukaemia present?
Bruising/bleeding (thrombocytopenia), pallor and fatigue (anaemia) and infection (neutropenia)
What gene translocations are commonly found in acute lymphoblastic leukaemia in children?
MLL or TEL-AML1
How does an MLL translocation acute lymphoblastic leukaemia affect prognosis?
This causes a pro-B cell acute lymphoblastic leukaemia which is unfavourable for prognosis
How does an TEL-AML1 translocation acute lymphoblastic leukaemia affect prognosis?
This causes a pre-B cell acute lymphoblastic leukaemia and causes hyperdiploidy (increased chromosome number) and is favourable to prognosis
What is a Wilms’ tumour?
A tumour of the kidney also known as a nephroblastoma
How does a Wilms’ tumour present?
Asymptomatic abdominal mass without metastases
What syndrome predisposes a child to developing a Wilms’ tumour?
Beckwith-Wiedeman Syndrome (chromosome 11)
Outline the pathophysiology of how WIlms’ tumours develop
Pluripotent embryonic renal precursor molecules divide rapidly , expressing markers of early kidney development
What somatic mutations may give rise to a Wilms’ tumour?
Inactivated WT1, WTX, TP53
Activated CTNNB1
What germline mutations may give rise to a Wilms’ tumour?
WT1 gene or IGF2 or H19 focus
What is a retinoblastoma?
A tumour of the retina
What are the symptoms of retinoblastoma?
Leukocoria (white pupil when light shone onto it), eye pain, redness and vision problems
What are the genetic cause of retinoblastoma?
Germline mutation of RB1 or MYCN gene OR amplification of MDM2/2 which leads to inactivation of the p53 pathway
What is the pathophysiology of the development of retinoblastoma?
Orginates from cone precursor cells in the retina
What is the role of RB1 and how is it implicated in the development of retinoblastoma?
Normally, phosphorylation of RB1 causes the release of E2F which induces transition into mitosis, however in cancer cells the lack of of RB1 leads to free E2F which induces transition into mitosis without the control of RB1
What is a neuroblastoma?
A tumour of the sympathetic nervous system, commonly arising in the adrenal gland or sympathetic ganglia
What is the most common cancer in the first year of life?
Neuroblastoma
What are the main genes implicated in the development of neuroblastoma?
MYCN, ALK and PHOX2B
What genetic defect is associated with Li-Fraumeni syndrome?
Germline mutation in TP53
