Cancer In Children Flashcards
Why can cancer have lifelong effects
Tumour effects
Chemo effects
Radio effects
Brain damage
Malignancies originating in developing tissues and organ systems
Wilms tumour
Retinoblastoma
Neuroblastoma
Acute lymphoblastic leukaemia
Medulloblastoma
Hepatoblastoma
Rhabdomyosarcoma
Germ cell tumours
What types of genetic alterations cause cancer
Mutations
Chromosome defects
Epigenetic changes
Do oncogenes and tumour suppressor genes cause cancer by gain or loss of function
Oncogenes - gain
Tumour suppressor genes - loss
How are oncogenes activated
Murptatiom
Chromosome translocation
Gene amplification
retro viral insertion
What type of genes are RB, WT1, TP53, PTCH1, BRCA1, BRCA2, APC, NF1
Tumour suppressor genes
What type of genes are MYCN, MDM2, ALK, ABL1, HRAS, KRAS, NRAS, BRAF
Oncogenes
How are tipumour suppressor genes inactivated
Mutation
Deletions
DNA methylation - epigenetic
Are oncogenes or tipumour suppressor genes dominant
Oncogenes - dominant - activation of 1 allele sufficient
Tumour suppressor genes - recessive - inactivation of both genes necessary
Wilms tumour
Nephroblastoma - Kidney tumour most common under 5 yrs
Wilms tumour presentation
Asymptomatic posterior abdominal mass without metastases
Wilms tumour predisposition syndromes
- WAGR - wilms tumour, aniridia, genitourinary abnormalities, mental retardation
- BWS - beckwith wiedeman syndrome
Denys d rash syndrome
Perlman syndrome
Franconi anaemia
Mosaic variegated aneuploidy
WT1 role and which cancer its alteration associated with
Ureteric branching, epithelial induction of metanephric mesenchyme
Wilms tumour
What cells does Wilms tumours develop from
Pluripotent embryonic renal precursors
Which cells are usually present in a Wilms tumour
Blastema
Epithelia
Stroma
How does WT1 absence cause cancer
Prevents differentiation and keep cells in an immature state leading to Wilms tumour
Wilms tumour treatment
Surgery
Chemo
Genetic counselling
Retinoblastoma
Tumour of retina
Retinoblastoma symptoms
Leukocoria
Eye pain
Eye redness
Vision problems
What ages are Wilms tumours and retinoblastoma most common in
Under 5s
Leukocoria
White reflection on pupil when light shone into eye
What cells does retinoblastoma originate from
Cone precursor cells
RB1 protein role in cell cycle
Keeps cells at G1 by Binding to E2F when Unphosphorylated, rb phosphorylation frees E2F inducing G1-S transition
What is the main genetic change causing retinoblastoma
loss of both RB1 alleles
Retinoblastoma treatment
Cryotherapy
Laser therapy
Thermotherapy
Chemo
Radio
Surgery
Neuroblastoma
Tumour of sympathetic nervous system usually arising in adrenal gland or sympathetic ganglia
When is Neuroblastoma most common
1st yr
How many cases of Neuroblastoma metastasise
> 1/2
4s to liver and skin
What cells does Neuroblastoma originate in
Sympatho adrenal lineage of the neural crest
Key genes in Neuroblastoma development
MYCN
ALK
PHOX2B
Neuroblastoma High risk molecular abnormalities
MYCN amplification
ATRX mutation
ALK mutation
Near-diploid/near-haploid karyotype
Chromosome aberrations1p and 11q deletions
Neuroblastoma treatment
Surgery
Chemo
Radio
Stem cell transplant
4s Can spontaneously regress
Crizotinib against ALK mutations
Immunotherapy
Chemo related complications
Hearing loss
Infertility
Cardiac toxicity
Second malignancies
Most common malignancy in children
Acute lymphoblastic leukaemia
Acute lymphoblastic leukaemia presentation
Bruising - thrombocytopenia
Bleeding - thrombocytopenia
Pallor - anaemia
Fatigue - anaemia
Infection - neutropenia
Most common areas of metastases of acute lymphoblastic leukaemia
Liver
Spleen
Lymph nodes
Mediastinum
Types of acute lymphoblastic leukaemia
Pro B cell ALL
Pre B cell ALL
T cell ALL
Acute lymphoblastic leukaemia origin
Lymphoblast Haematopoiesis
Why are both children in a pair of identical twins likely to get cancer if 1 gets it
Shared blood supply in utero means both can get a first hit
How are ALL patients separated into risk groups
Clinical features
Biological features
Genetic features
ALL treatment
Induction - vincristine, corticosteroid, L asparaginase, anthracycline
Consolidation - targets CNS - cyclophosphamide, cytarabine, mercaptopurine, methotrexate, dexamethasone
Maintainance - mercaptopurine, methotrexate
Bone marrow transplant
What is consolidation treatment for ALL targeted at
CNS
Predispositions to childhood cancer
Cancer diagnosed in perinatal period
Bilateral of multi focal disease
Cancer in close relatives
Same rare tumour in >1 family member
Different types of tumour in family members
Genetic predisposition syndromes for childhood cancers
WAGR
beckwith Weideman
Familial retinoblastoma
Familial Neuroblastoma
Basal cell Nevis
Li fraumeni
