Cancer in Children Flashcards
What are the most common cancers in 0-14 years?
- leukaemia
- CNS
- lymphomas
What are the most common cancer in 15-19 years?
- lymphomas
- carcinomas and melanomas
- CNS
- leukaemia
What is the problem with chemotherapy and radiation with children?
- chemo -> toxic in children as many dividing cells
- radiation -> damage growing cells leading to development of other tumours
What is cancer?
- mutation of the genome
- accumulation of genetic abberations in somatic cells consisting of mutations and chromosome defects
- lead to altered gene expression
What are oncogenes?
- dominant (1 allele activated needs to be present)
- act by gain of function
- encode protein capable of inducing cancer
What are oncogenes activated by?
- mutation
- chromosome translocation
- gene amplification
- retroviral insertion
What are tumour suppressor genes?
- act by loss of function
- recessive (2 inactivated alleles need to be present)
- cause genetic predisposition in cancer
What are tumour suppressor genes inactivated by?
- mutations
- deletions
- DNA methylation
What is the clinical presentation of Wilms tumour?
- aggressive tumour of kidney
- nephroblastoma
- asymptomatic abdominal mass without metastasis
- spreads via growth or lymph/blood
What is Wilms syndrome associated with?
- Aniradia
- Genito-urinary abnormalities
- Mental retardation
- Beckwith-Wiedeman syndrome
What are the cellular origins of WIlm’s tumour?
- pluripotent embryonic renal precursors
- resembles nephrogenic mesenchyme
- contains blasterma, epithelia, stroma (3 cell types in embryonic kidney)
What are the somatic genetic alterations of Wilm’s tumour?
- inactivated WT1, WTX, TP53 genes
- activated beta catenin (oncogene)
- epigenetic alterations at IGF2/H19 locus
- cells kept in embryonic state and proliferate
What is the key role of WT1 in Wilm’s tumour?
- ureteric branching
- activated by beta catenin
- epithelial induction of metanephric mesenchyme
How is Wilm’s tumour treated?
- surgery then chemo (or vice versa)
- radiotherapy use decreasing
What is the clinical presentation of retinoblastoma?
- retina tumour
- leukocoria (white pupil when light shone into it)
- eye pain
- redness
- vision problems
What are the cellular origins of retinoblastoma?
- originates from cone precursor cells
- signalling pathways promote cell survival after RB1 loss
What is the role of RB1? **
- 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
How is retinoblastoma treated?
- small tumours = cryotherapy, laser, thermotherapy
- more advanced = chemotherapy, surgery, radiation
(chemotherapy shrinks tumour before cryotherapy and laser)
What is the presentation of neuroblastoma?
- SymNS tumour arising in adrenal gland/sympathetic ganglia
- many metastasise to liver and skin via N4S
What are the cellular origins of neuroblastoma?
- derived from sympatho-adrenal linage of neural crest during development
- originates from incompletely committed precursor cell
- key genes are MYCN and ALK and PHOX2B
What is the pathology of high risk neuroblastoma?
- MYCN amplification (TF)
- ATRX and ALK mutations
What is the pathology of low risk/intermediate neuroblastoma?
- numerical chromosomal gains
What is the pathology of hereditary neuroblastoma?
- germline ALK mutations
How is neuroblastoma treated?
- high risk = high dose chemo and stem cell transplantation
- targeted therapy = crizotinib against ALK mutations
- immunotherapy
What are some complications of chemotherapy on neuroblastoma?
- hearing loss
- infertility
- cardiotoxicity
How is acute lymphoblastic leukaemia clinically presented?
- most common malignancy in children
- bruising/bleeding
- pallor/fatigue due to anaemia
- infection as neutropenia
- clonal expansion of immature lymphocytes
What are the cellular origins of leukaemia?
- haematopoiesis
- CD19+ on cell surface
- CD19+ and CD10+
- have specific genetic changes causing different leukaemia types
What are the standard treatment phases for leukaemia?
- induction
- consolidation
- maintenance
- bone marrow transplantation
Who are high risk groups for cancer?
- 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)
What are the stages of Wilm’s tumour?
- invasion of ureteric bud
- condensation
- comma shape formation
- S shape
- tubule elongation
- nephron maturation
What is a bilateral tumour indicative of?
Hereditary disposition
If just 1 - preserve function of other kidney
