ch 28 genes Flashcards
ATM gene is mutated (11q22-q23)
Ataxia-telangiectasia
-encodes the kinase that helps with DS DNA breaks and many other cellular housekeeping functions
overexpression of the receptor for PDGFRA
proneural subtype of infiltrating astrocytomas
-increasedRTK signaling
mutations in PTEN (TS gene)
classic subtype of infiltrating astrocytomas
BRAF mutations
- Pilocytic astrocytoma
- Gangliogliomas (this will cause them to return
- Translocations that separate the kinase domain from the inhibitory domain
mutation in TNF receptor 7 (TNFR7)
meningiomas
metation on PA1 on chromo 14 and PS2 on chromo 1
encode presenilins: GoF in y-secretase => increased AB –> Alzheimers Dis
deletions of chr 10
classic subtype of infiltrating astrocytomas
Defect in the gene encoding for progranulin
FTLD-TDP
- NOT assoc w ALS
- linked w inflamm
overexpression of genes in the TNF and NF-kB pathways
mesenchymal type of infiltrating astrocytomas
mutations in WNT and monosomy of chr 6
WNT type medullobalstoma
mutations in hSNF5/INI1 (chr 22).
Atypical teratoid/rhabdoid tumors
Defect in intermediate filament proteins like GFAP
Alexander dz
Defect in gene coding for myelin formation.
Pelizaeus-Merzbacher dz
The AV4 missense mutation of SOD1
most common mutation that leads to ALS
deletions of the NF1 gene on chr 17
mesenchymal type of infiltrating astrocytomas
-lower expression of the NF1 protein
hexanucleotide repeat in the 5’ UTR of C9orf72
FTLD-TDP
-also assoc w ALS
K27M (lys to met) mutation in histone H3.1 or H3.3.
Brainstem glioma
mutations in PTEN resulting in PI3K/AKT signaling activity
Cowden syndrome
-Dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos Dz
auto rec deficiency of the lysosomal enzyme arylsulfatase A
Metachromatic leukodystrophy
-build up of sulfatides
High levels of expression of neuronal markers: NEFL, GABRA1, SYT1, SLC12A5
Neural type of infiltrating astrocytomas
defects in DJ-1, PINK1, and parkin
Auto rec forms of PD
-cause mito probs
isochromosome 17 (i17q) and no MYC amplification
Group 4 Medulloblastoma
-Mutation in i17q makes a medulloblastoma more resistant to chemo &worse prognosis
mutations in the PTCH gene resulting in up regulation of SHH
Gorlin syndrome
-cause Medulloblastoma
PNRP gene at residue 178:
If at codon 129 causes methionine in tandem with valine =
CJD
FUS
FTLD-FUS
-also assoc w ALS
Auto rec leukodystrophy from a defect in galactosylceramidase
Krabbe dis
mutations of TP53
- proneural subtype of infiltrating astrocytomas
- Li-Fraumeni Syndrome: cause Medulloblastomas
mutated MF2 gene in spinal cord, but not in other places
Ependymomas
X-linked polyglutamine repeat expansion in the androgen receptor
Spinal and bulbar muscular atrophy (Kennedy dz)
Expansion of GAA trinucleotide repeat for the mito protein frataxin (9q13).
Friedreich ataxia
- Clinical features correlate with the amount of frataxin present as fraxaxin is needed for oxphos.
- more free Fe in the mito with less frataxin that can lead to more oxidative damge.
SMN1 deletion or SMN2 copy # varaition
Spinal muscular atrophy SMA type III (kugelberg-welander dz)
–creates for an unstable protein
PNRP gene at residue 178:
If at codon 129 causes methionine =
-Fatal familial insomnia (FFI)
α-syn is mutated (chr 4q21)
autosomal dominant Parkinsons dis
- a Lipid-binding protein assoc w synapses, pt mutations, and amplifications
point mutations in IDH1 and IDH2
proneural subtype of infiltrating astrocytomas AND oligodendrogliomas
- in the lower grade II/III glioblastomas.
- IDH1 assoc w better prognosis in glioblastomas grades III and IV
- in oligodendroglioma, if have1p and 19q co-deleiton: more sensative to chemo
amplification of the EGFR oncogene (increases RTK signaling)
classic subtype of infiltrating astrocytomas
-not have this in oligodendrogliomas: how can tell apart
TSC1 (hamartin on chr 9q34) and TSC2 (tuberin on chr 16p13.3) are mutated
Tuberous sclerosis complex
-preventing mTOR (which normally controls cell size)
loss of the NF2 gene on chr 22 that encodes for merlin
meningiomas
mutations in APC or mismatch repair genes
Turcot syndrome
-cause Medulloblastoma or glioblastoma
Mutation/extra copy in APP
familial Alzheimers Dis
Defect in genes for subunits of translation initiation factor eIF2B
Vanishing white matter leukoencephalopathy
mutation is in the gene encoding mito tRNA-leucine (MTTL1)
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS)
GoF in LRRK2
autosomal dominant Parkinsons dis
-a cytoplasmic kinase: gains fct to hyperphosphoryate Tau –> not bind MTs –> aggregates
CAG expansion in SCA1, SCA2, SCA3 (Machado-Joseph dz), SCA6, SCA7 (vision impairment too), SCA17
Spinocerebellar ataxias (SCAs)
defect in apolipoprotein E (ApoE) locus on Chr 19, esp in the ε4 allele
- Increases the risk and lower the age of onset of Alzheimers Dis
- Promotes AB generation and deposition
trinucleotide repeat expansion : of CAG repeats at the N terminus of
-HTT on chr 4p16.
Huntingtons Dis
- inverse relationship between the number of repeats and the age of onset.
- huntingtin protein
focal deletions of 9p21 (hemizygous del of CDKN2A)
classic subtype of infiltrating astrocytomas AND oligodendrogliomas
mutation with the VHL gene (3p25.3) that normal inhibits HIF-1
Von Hippel-Lindau ds
Defect (LoF or GoF) in the TDP-43 gene
FTLD-TDP
-also assoc w ALS
MYC amplification and isochromosome 17 (i17q)
Group 3 Medulloblastoma
-Mutation in i17q makes a medulloblastoma more resistant to chemo &worse prognosis
defects in sonic hedgehog
-May have MYCN amplification
SHH type medullobalstoma
X linked rec mutation in the ATP binding cassette transporter family of proteins (ABCD1) that transports molecules into the peroxisome.
Adrenoleukodystrophy
