Cancer in children Flashcards
Most Common Cancers 0-14 years
Leukaemia (31.1%)
CNS (25.4%)
Lymphomas (10%)
Most Common Cancers 15-19 years
Lymphomas (20.7%)
Carcinomas + Melanoma (19.6%)
CNS (18.7%)
Leukaemia (13.8%)
Chemotherapy
Especially toxic in children as have many dividing cells
Radiation
Can damage growing cells + lead to development of other tumours
Oncogenes
Genes that encode protein capable of inducing cancer
Dominant
Act by gain of function
Activated by- mutation, chromosome translocation, gene amplification, retroviral insertion
Tumour suppressor genes
Act by loss of function
Recessive
Inactivated by mutations, deletions, DNA methylations
Cause genetic predisposition to cancer
Wilms Tumour
Aggressive tumour of kidney
Usually asymptomatic abdominal mass without metastasis
Arises from pluripotent embryonic renal precursors
Wilms Tumour cells
Classically contains Blastema, Epithelia and stroma
Resembles developing nephrogenic mesenchyme
Wilms tumour molecular pathology
Inactivated WT1, WTX and TP53 genes
WT1
Key role in ureteric branching
WT1/WNT activated by beta catenin
If don’t have WT1, no differentiation - no nephron
Wilms tumour treatment
Surgery then Chemo
Retinoblastoma
Tumour of retina
RB1 gene
Metastatic 10-15%
Leukoria (white pupil when light shone into it), eye pain or redness, vision problems
Cell origins Retinoblastoma
Originates from cone precursor cells
Signalling pathways promote cell survival after loss of RB1
RB1 Role
Phosphorylation of RB1 critical to allow cells to move through cycle
Unphosphorylated RB1 binds to E2F
Releases E2F if phosphorylated, inducing G1-S transition
Cells without RB1
If don’t have RB1, E2F free to induce G1-S transition whenever
RB1 treatment
Small tumours- cryotherapy, laser therapy, thermotherapy
More advanced- chemo, surgery or radiation
Neuroblastoma
Tumour of SymNS, usually arising from adrenal gland/symp. ganglia
N4S- metastatic disease to liver and skin
Neuroblastoma cellular origin
Derived from sympatho-adrenal linage of neural crest during development
Key genes- MYCN, ALK
High risk Neuroblastoma
MYCN amplification (transcription factor- causes proliferation), ATRX, ALK mutations
Hereditary neuroblastoma
germline ALK mutations
Neuroblastoma targeted therapy
Crizotinib against ALK mutations
Acute lymphoblastic leukaemia
Most common malignancy in children Bruising/bleeding Pallor or fatigue due to anaemia Infection due to neutropenia Clonal expansion of immature lymphocytes
ALL molecular pathology
MLL translocation (CD 19+ on cell surface, Pro-B)- unfavourable More favourable- TEL-AML1 translocation (19 and 10)
