Cancer in Children

Question 1

What are the most common cancers in 0-14 years?

Answer 1

• leukaemia
• CNS
• lymphomas

Question 2

What are the most common cancer in 15-19 years?

Answer 2

• lymphomas
• carcinomas and melanomas
• CNS
• leukaemia

Question 3

What is the problem with chemotherapy and radiation with children?

Answer 3

• chemo -> toxic in children as many dividing cells

- radiation -> damage growing cells leading to development of other tumours

Question 4

What is cancer?

Answer 4

• mutation of the genome
• accumulation of genetic abberations in somatic cells consisting of mutations and chromosome defects
• lead to altered gene expression

Question 5

What are oncogenes?

Answer 5

• dominant (1 allele activated needs to be present)
• act by gain of function
• encode protein capable of inducing cancer

Question 6

What are oncogenes activated by?

Answer 6

• mutation
• chromosome translocation
• gene amplification
• retroviral insertion

Question 7

What are tumour suppressor genes?

Answer 7

• act by loss of function
• recessive (2 inactivated alleles need to be present)
• cause genetic predisposition in cancer

Question 8

What are tumour suppressor genes inactivated by?

Answer 8

• mutations
• deletions
• DNA methylation

Question 9

What is the clinical presentation of Wilms tumour?

Answer 9

• aggressive tumour of kidney
• nephroblastoma
• asymptomatic abdominal mass without metastasis
• spreads via growth or lymph/blood

Question 10

What is Wilms syndrome associated with?

Answer 10

• Aniradia
• Genito-urinary abnormalities
• Mental retardation
• Beckwith-Wiedeman syndrome

Question 11

What are the cellular origins of WIlm’s tumour?

Answer 11

• pluripotent embryonic renal precursors
• resembles nephrogenic mesenchyme
• contains blasterma, epithelia, stroma (3 cell types in embryonic kidney)

Question 12

What are the somatic genetic alterations of Wilm’s tumour?

Answer 12

• inactivated WT1, WTX, TP53 genes
• activated beta catenin (oncogene)
• epigenetic alterations at IGF2/H19 locus
• cells kept in embryonic state and proliferate

Question 13

What is the key role of WT1 in Wilm’s tumour?

Answer 13

• ureteric branching
• activated by beta catenin
• epithelial induction of metanephric mesenchyme

Question 14

How is Wilm’s tumour treated?

Answer 14

• surgery then chemo (or vice versa)

- radiotherapy use decreasing

Question 15

What is the clinical presentation of retinoblastoma?

Answer 15

• retina tumour
• leukocoria (white pupil when light shone into it)
• eye pain
• redness
• vision problems

Question 16

What are the cellular origins of retinoblastoma?

Answer 16

• originates from cone precursor cells

- signalling pathways promote cell survival after RB1 loss

Question 17

What is the role of RB1? **

Answer 17

• retinoblastoma
• in normal cells RB1 gets phosphorylated allowing cells to move through cycle
• in cancer cells no RB1 so E2F released inducing G1-S transition
• also activates MYCN for proliferation

Question 18

How is retinoblastoma treated?

Answer 18

• small tumours = cryotherapy, laser, thermotherapy
• more advanced = chemotherapy, surgery, radiation

(chemotherapy shrinks tumour before cryotherapy and laser)

Question 19

What is the presentation of neuroblastoma?

Answer 19

• SymNS tumour arising in adrenal gland/sympathetic ganglia

- many metastasise to liver and skin via N4S

Question 20

What are the cellular origins of neuroblastoma?

Answer 20

• derived from sympatho-adrenal linage of neural crest during development
• originates from incompletely committed precursor cell
• key genes are MYCN and ALK and PHOX2B

Question 21

What is the pathology of high risk neuroblastoma?

Answer 21

• MYCN amplification (TF)

- ATRX and ALK mutations

Question 22

What is the pathology of low risk/intermediate neuroblastoma?

Answer 22

• numerical chromosomal gains

Question 23

What is the pathology of hereditary neuroblastoma?

Answer 23

• germline ALK mutations

Question 24

How is neuroblastoma treated?

Answer 24

• high risk = high dose chemo and stem cell transplantation
• targeted therapy = crizotinib against ALK mutations
• immunotherapy

Question 25

What are some complications of chemotherapy on neuroblastoma?

Answer 25

• hearing loss
• infertility
• cardiotoxicity

Question 26

How is acute lymphoblastic leukaemia clinically presented?

Answer 26

• most common malignancy in children
• bruising/bleeding
• pallor/fatigue due to anaemia
• infection as neutropenia
• clonal expansion of immature lymphocytes

Question 27

What are the cellular origins of leukaemia?

Answer 27

• haematopoiesis
• CD19+ on cell surface
• CD19+ and CD10+
• have specific genetic changes causing different leukaemia types

Question 28

What are the standard treatment phases for leukaemia?

Answer 28

• induction
• consolidation
• maintenance
• bone marrow transplantation

Question 29

Who are high risk groups for cancer?

Answer 29

• tumour diagnosed in perinatal period suggests genetic predisposition syndrome
• bilateral/multifocal disease associated with congenital malformations
• cancer in close relatives
• same rare tumour in more than 1 family member (retinoblastoma)

Question 30

What are the stages of Wilm’s tumour?

Answer 30

• invasion of ureteric bud
• condensation
• comma shape formation
• S shape
• tubule elongation
• nephron maturation

Question 31

What is a bilateral tumour indicative of?

Answer 31

Hereditary disposition

If just 1 - preserve function of other kidney