Cancer in Children

Question 1

Name the four most common cancers to affect children under the age of 5.

Answer 1

Acute lymphoblastic leukaemia (ALL), WIlms’ tumour, retinoblastoma and neuroblastoma

Question 2

What is the most common cancer that presents in children under the age of 5?

Answer 2

Acute lymphoblastic leukaemia

Question 3

How may a child with acute lymphoblastic leukaemia present?

Answer 3

Bruising/bleeding (thrombocytopenia), pallor and fatigue (anaemia) and infection (neutropenia)

Question 4

What gene translocations are commonly found in acute lymphoblastic leukaemia in children?

Answer 4

MLL or TEL-AML1

Question 5

How does an MLL translocation acute lymphoblastic leukaemia affect prognosis?

Answer 5

This causes a pro-B cell acute lymphoblastic leukaemia which is unfavourable for prognosis

Question 6

How does an TEL-AML1 translocation acute lymphoblastic leukaemia affect prognosis?

Answer 6

This causes a pre-B cell acute lymphoblastic leukaemia and causes hyperdiploidy (increased chromosome number) and is favourable to prognosis

Question 7

What is a Wilms’ tumour?

Answer 7

A tumour of the kidney also known as a nephroblastoma

Question 8

How does a Wilms’ tumour present?

Answer 8

Asymptomatic abdominal mass without metastases

Question 9

What syndrome predisposes a child to developing a Wilms’ tumour?

Answer 9

Beckwith-Wiedeman Syndrome (chromosome 11)

Question 10

Outline the pathophysiology of how WIlms’ tumours develop

Answer 10

Pluripotent embryonic renal precursor molecules divide rapidly , expressing markers of early kidney development

Question 11

What somatic mutations may give rise to a Wilms’ tumour?

Answer 11

Inactivated WT1, WTX, TP53

Activated CTNNB1

Question 12

What germline mutations may give rise to a Wilms’ tumour?

Answer 12

WT1 gene or IGF2 or H19 focus

Question 13

What is a retinoblastoma?

Answer 13

A tumour of the retina

Question 14

What are the symptoms of retinoblastoma?

Answer 14

Leukocoria (white pupil when light shone onto it), eye pain, redness and vision problems

Question 15

What are the genetic cause of retinoblastoma?

Answer 15

Germline mutation of RB1 or MYCN gene OR amplification of MDM2/2 which leads to inactivation of the p53 pathway

Question 16

What is the pathophysiology of the development of retinoblastoma?

Answer 16

Orginates from cone precursor cells in the retina

Question 17

What is the role of RB1 and how is it implicated in the development of retinoblastoma?

Answer 17

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

Question 18

What is a neuroblastoma?

Answer 18

A tumour of the sympathetic nervous system, commonly arising in the adrenal gland or sympathetic ganglia

Question 19

What is the most common cancer in the first year of life?

Answer 19

Neuroblastoma

Question 20

What are the main genes implicated in the development of neuroblastoma?

Answer 20

MYCN, ALK and PHOX2B

Question 21

What genetic defect is associated with Li-Fraumeni syndrome?

Answer 21

Germline mutation in TP53