24 - Brain Cancer Flashcards
Cerebrum
- Cerebral cortex, basal ganglia, olfactory bulb
- Thinking, learning, emotion, speech
Cerebellum
Movement, balance, posture
Diencephalon
- Thalamus, hypothalamus
- endocrine system, sensory input, sleep
Brain Stem
- Pons, substantia nigra, medulla oblongata
- Connects brain to spinal cord
- Breathing, heart rate
Frontal lobe
- Movement
- Memory
- Decision making
- Planning
Temporal lobe
- Language
- Hearing
- Emotions
Parietal lobe
- Sensations
- Reading
- Writing
- Calculations
Occipital lobe
Vision
Are primary or metastatic tumours more common in brain
Metastatic
Malignant brain tumours
Very rarely spread to other areas of the body, but can spread throughout the brain or spine
How are brain cancers classified
- The cells from which they arise
- Molecular features
- Grade
Locations brain tumours arise
- Brain
- Pineal and pituitary glands
- Cranial nerves
- Meninges
- Spinal cord
Types of cells in the mammalian brain
- Neurons
- Oligodendrocytes
- Microglia
- Astrocytes
- Ependymal cells
How many tumour classifications have been defined by the WHO
Over 120 CNS tumours
Example of histologic types of brain tumours
- Astrocytoma
- Glioblastoma
- Ependymoma
- Meningioma
- Medulloblastoma
Brain tumour locations
- Supratentorial
- Infratentorial
- Spinal
- Intra-axial
- Extra-axial (e.g. in CSF, meninges)
Most common cancers
among children aged 0–14 years
- Brain and other CNS tumors
- Most are are not malignant in adults, but are in children
Grade I
- Slow growing
- Histologically almost normal
Grade II
- Relatively slow growing cells
- Slightly abnormal histology
Grade III
- Actively reproducing abnormal cells
- Abnormal appearance
- Infiltration into adjacent tissue
Grade IV
- Abnormal cells producing rapidly
- Very abnormal microscopic appearance
- Angiogenesis
DNA methylation
- Addition of a methyl group to cytosine at CpG islands (regions of the genome with high frequency of CG sites)
- Inhibits transcription by preventing access to promoters
Bisulfite conversion of genomic DNA
- Converts C to U
- Methylation protects C from conversion
Illumina DNA methylation arrays
- C not methylated and converted to T, Complementary base is “red”
- C was methylated and not converted, Complementary base is “green
Gliomas
- Most common primary brain tumour
- Originate from glial cells
- Include ependymomas, astrocytomas
Which tumours account for 25-30% of childhood brain tumours
Low grade gliomas
Glioblastoma (WHO Grade IV)
- Symptoms are usually non specific (headaches, personality changes, nausea, similar to a stroke)
- No known causes
- Surgery chemo, focal radiation
- Survival 14 months with treatment
Risk factors of glioblastoma
- Genetic disorders
- Previous radiation therapy or exposure to ionising radiation
Glioblastoma IDH1 status
- Prognostic marker
- Mutation associated with increased overall survival
IDH1
- Isocitrate dehydrogenase
- Normally produces a-ketoglutarate
Mutant IDH1
- Gain-of-function
- Produces D-2- hydroxyglutarate (2HG)
- 2HG accumulates up to mM concentrations & results in changes to the
epigenetic landscape of the tumour
Ependymoma
- Affects all ages
- Arise from ependymal cells that form the lining of the ventricles
- Never grade IV
- Arise in Supratentorial, posterior fossa, spinal cord
- 10 molecular subgroups
Medulloblastoma
- Most common malignant brain tumour of childhood
- Arise in cerebellum
- Incidence decreases with age (Cerebellum growing when young)
- More common in boys than girls
- 4 molecular subtypes
Medulloblastoma risk factors
- Gorlin syndrome (PTCH)
- Li-Fraumeni syndrome (TP53)
- Familial Adenomatous Polyposis (APC)
Recurrent genetic mutations in medulloblastoma
- WNT (b-catenin activation)
- SHH (Gli2 amplification)
- Group 3 (MYC amplification)
- Group 4 (KDM6A mutation)
Medulloblastoma Treatment
- Surgery
- Multiagent chemotherapy
- Cranio-spinal radiation therapy
% of all tumours that brain tumours make up
10%
