Cancer in children

Question 1

Most Common Cancers 0-14 years

Answer 1

Leukaemia (31.1%)
CNS (25.4%)
Lymphomas (10%)

Question 2

Most Common Cancers 15-19 years

Answer 2

Lymphomas (20.7%)
Carcinomas + Melanoma (19.6%)
CNS (18.7%)
Leukaemia (13.8%)

Question 3

Chemotherapy

Answer 3

Especially toxic in children as have many dividing cells

Question 4

Radiation

Answer 4

Can damage growing cells + lead to development of other tumours

Question 5

Oncogenes

Answer 5

Genes that encode protein capable of inducing cancer
Dominant
Act by gain of function
Activated by- mutation, chromosome translocation, gene amplification, retroviral insertion

Question 6

Tumour suppressor genes

Answer 6

Act by loss of function
Recessive
Inactivated by mutations, deletions, DNA methylations
Cause genetic predisposition to cancer

Question 7

Wilms Tumour

Answer 7

Aggressive tumour of kidney
Usually asymptomatic abdominal mass without metastasis
Arises from pluripotent embryonic renal precursors

Question 8

Wilms Tumour cells

Answer 8

Classically contains Blastema, Epithelia and stroma

Resembles developing nephrogenic mesenchyme

Question 9

Wilms tumour molecular pathology

Answer 9

Inactivated WT1, WTX and TP53 genes

Question 10

WT1

Answer 10

Key role in ureteric branching
WT1/WNT activated by beta catenin
If don’t have WT1, no differentiation - no nephron

Question 11

Wilms tumour treatment

Answer 11

Surgery then Chemo

Question 12

Retinoblastoma

Answer 12

Tumour of retina
RB1 gene
Metastatic 10-15%
Leukoria (white pupil when light shone into it), eye pain or redness, vision problems

Question 13

Cell origins Retinoblastoma

Answer 13

Originates from cone precursor cells

Signalling pathways promote cell survival after loss of RB1

Question 14

RB1 Role

Answer 14

Phosphorylation of RB1 critical to allow cells to move through cycle
Unphosphorylated RB1 binds to E2F
Releases E2F if phosphorylated, inducing G1-S transition

Question 15

Cells without RB1

Answer 15

If don’t have RB1, E2F free to induce G1-S transition whenever

Question 16

RB1 treatment

Answer 16

Small tumours- cryotherapy, laser therapy, thermotherapy

More advanced- chemo, surgery or radiation

Question 17

Neuroblastoma

Answer 17

Tumour of SymNS, usually arising from adrenal gland/symp. ganglia
N4S- metastatic disease to liver and skin

Question 18

Neuroblastoma cellular origin

Answer 18

Derived from sympatho-adrenal linage of neural crest during development
Key genes- MYCN, ALK

Question 19

High risk Neuroblastoma

Answer 19

MYCN amplification (transcription factor- causes proliferation), ATRX, ALK mutations

Question 20

Hereditary neuroblastoma

Answer 20

germline ALK mutations

Question 21

Neuroblastoma targeted therapy

Answer 21

Crizotinib against ALK mutations

Question 22

Acute lymphoblastic leukaemia

Answer 22

Most common malignancy in children
Bruising/bleeding
Pallor or fatigue due to anaemia
Infection due to neutropenia
Clonal expansion of immature lymphocytes

Question 23

ALL molecular pathology

Answer 23

MLL translocation (CD 19+ on cell surface, Pro-B)- unfavourable
More favourable- TEL-AML1 translocation (19 and 10)