Neuroblastomas Flashcards
What is their origin
Neural crest cells
Form tumours anywhere along the sympathetic genglion
What 3 factors are inovlved in the staging of neuroblatcom
Age
MYCN Status
Histology
What are the ways that might explain spontaneous regression in neuroblastomas
1) Neurotophin deprivation
2) Immune mediated cell killing
3) Telomere shortening
4) Epigenetic changes
What % of neuroblastomas are inherited
2%
What mutations are common in inherited neuroblastomas
ALK- 50%
PHOX2B
NF1
What somatic mutations are common in neuroblastomas
ALK MYCN amplification ATRX LOMO1 NF1
How is ALK activated in somatic neuroblastomas
t(2:5) but ALK near the MYCN locus
What is often epigenetically silenced in neuroblastomas
Caspase 8
What genetic changes are often seen in NB
Few recurrent a.a. acid changes but often see Chromothripsis Eigenetic Changes Neuritogenic gene defects Clustered changes in high risk tumours
What gene is often related in relation to telomeres in NB
TERT Gene on CHr 5 is put next to strong enhancers –> massively upregulated.
List some therapies for NB
MIBG Immunotherapy Retinoids ALK MYCN Regulators
What are the paraneoplastic syndromes in NB
Watery Diarrhoea
Opsonos-Myoclonos Syndrome
What neurotrophin pathway shows a favourable NB prognosis
High TKRA
What does immmunotherapy want to target in NB
G52 disialoganglioside –> anti-GD2 mABS can target this
What is a limiting SE of G52 mABs
Pain
