ch 28 genes

Question 1

ATM gene is mutated (11q22-q23)

Answer 1

Ataxia-telangiectasia

-encodes the kinase that helps with DS DNA breaks and many other cellular housekeeping functions

Question 2

overexpression of the receptor for PDGFRA

Answer 2

proneural subtype of infiltrating astrocytomas

-increasedRTK signaling

Question 3

mutations in PTEN (TS gene)

Answer 3

classic subtype of infiltrating astrocytomas

Question 4

BRAF mutations

Answer 4

• Pilocytic astrocytoma
• Gangliogliomas (this will cause them to return
• Translocations that separate the kinase domain from the inhibitory domain

Question 5

mutation in TNF receptor 7 (TNFR7)

Answer 5

meningiomas

Question 6

metation on PA1 on chromo 14 and PS2 on chromo 1

Answer 6

encode presenilins: GoF in y-secretase => increased AB –> Alzheimers Dis

Question 7

deletions of chr 10

Answer 7

classic subtype of infiltrating astrocytomas

Question 8

Defect in the gene encoding for progranulin

Answer 8

FTLD-TDP

• NOT assoc w ALS
• linked w inflamm

Question 9

overexpression of genes in the TNF and NF-kB pathways

Answer 9

mesenchymal type of infiltrating astrocytomas

Question 10

mutations in WNT and monosomy of chr 6

Answer 10

WNT type medullobalstoma

Question 11

mutations in hSNF5/INI1 (chr 22).

Answer 11

Atypical teratoid/rhabdoid tumors

Question 12

Defect in intermediate filament proteins like GFAP

Answer 12

Alexander dz

Question 13

Defect in gene coding for myelin formation.

Answer 13

Pelizaeus-Merzbacher dz

Question 14

The AV4 missense mutation of SOD1

Answer 14

most common mutation that leads to ALS

Question 15

deletions of the NF1 gene on chr 17

Answer 15

mesenchymal type of infiltrating astrocytomas

-lower expression of the NF1 protein

Question 16

hexanucleotide repeat in the 5’ UTR of C9orf72

Answer 16

FTLD-TDP

-also assoc w ALS

Question 17

K27M (lys to met) mutation in histone H3.1 or H3.3.

Answer 17

Brainstem glioma

Question 18

mutations in PTEN resulting in PI3K/AKT signaling activity

Answer 18

Cowden syndrome

-Dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos Dz

Question 19

auto rec deficiency of the lysosomal enzyme arylsulfatase A

Answer 19

Metachromatic leukodystrophy

-build up of sulfatides

Question 20

High levels of expression of neuronal markers: NEFL, GABRA1, SYT1, SLC12A5

Answer 20

Neural type of infiltrating astrocytomas

Question 21

defects in DJ-1, PINK1, and parkin

Answer 21

Auto rec forms of PD

-cause mito probs

Question 22

isochromosome 17 (i17q) and no MYC amplification

Answer 22

Group 4 Medulloblastoma

-Mutation in i17q makes a medulloblastoma more resistant to chemo &worse prognosis

Question 23

mutations in the PTCH gene resulting in up regulation of SHH

Answer 23

Gorlin syndrome

-cause Medulloblastoma

Question 24

PNRP gene at residue 178:

If at codon 129 causes methionine in tandem with valine =

Answer 24

CJD

Question 25

FUS

Answer 25

FTLD-FUS | -also assoc w ALS

Question 26

Auto rec leukodystrophy from a defect in galactosylceramidase

Answer 26

Krabbe dis

Question 27

mutations of TP53

Answer 27

- proneural subtype of infiltrating astrocytomas | - Li-Fraumeni Syndrome: cause Medulloblastomas

Question 28

mutated MF2 gene in spinal cord, but not in other places

Answer 28

Ependymomas

Question 29

X-linked polyglutamine repeat expansion in the androgen receptor

Answer 29

Spinal and bulbar muscular atrophy (Kennedy dz)

Question 30

Expansion of GAA trinucleotide repeat for the mito protein frataxin (9q13).

Answer 30

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.

Question 31

SMN1 deletion or SMN2 copy # varaition

Answer 31

Spinal muscular atrophy SMA type III (kugelberg-welander dz) | --creates for an unstable protein

Question 32

PNRP gene at residue 178: | If at codon 129 causes methionine =

Answer 32

-Fatal familial insomnia (FFI)

Question 33

α-syn is mutated (chr 4q21)

Answer 33

autosomal dominant Parkinsons dis | - a Lipid-binding protein assoc w synapses, pt mutations, and amplifications

Question 34

point mutations in IDH1 and IDH2

Answer 34

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

Question 35

amplification of the EGFR oncogene (increases RTK signaling)

Answer 35

classic subtype of infiltrating astrocytomas | -not have this in oligodendrogliomas: how can tell apart

Question 36

TSC1 (hamartin on chr 9q34) and TSC2 (tuberin on chr 16p13.3) are mutated

Answer 36

Tuberous sclerosis complex | -preventing mTOR (which normally controls cell size)

Question 37

loss of the NF2 gene on chr 22 that encodes for merlin

Answer 37

meningiomas

Question 38

mutations in APC or mismatch repair genes

Answer 38

Turcot syndrome | -cause Medulloblastoma or glioblastoma

Question 39

Mutation/extra copy in APP

Answer 39

familial Alzheimers Dis

Question 40

Defect in genes for subunits of translation initiation factor eIF2B

Answer 40

Vanishing white matter leukoencephalopathy

Question 41

mutation is in the gene encoding mito tRNA-leucine (MTTL1)

Answer 41

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS)

Question 42

GoF in LRRK2

Answer 42

autosomal dominant Parkinsons dis | -a cytoplasmic kinase: gains fct to hyperphosphoryate Tau --> not bind MTs --> aggregates

Question 43

CAG expansion in SCA1, SCA2, SCA3 (Machado-Joseph dz), SCA6, SCA7 (vision impairment too), SCA17

Answer 43

Spinocerebellar ataxias (SCAs)

Question 44

defect in apolipoprotein E (ApoE) locus on Chr 19, esp in the ε4 allele

Answer 44

- Increases the risk and lower the age of onset of Alzheimers Dis - Promotes AB generation and deposition

Question 45

trinucleotide repeat expansion : of CAG repeats at the N terminus of -HTT on chr 4p16.

Answer 45

Huntingtons Dis - inverse relationship between the number of repeats and the age of onset. - huntingtin protein

Question 46

focal deletions of 9p21 (hemizygous del of CDKN2A)

Answer 46

classic subtype of infiltrating astrocytomas AND oligodendrogliomas

Question 47

mutation with the VHL gene (3p25.3) that normal inhibits HIF-1

Answer 47

Von Hippel-Lindau ds

Question 48

Defect (LoF or GoF) in the TDP-43 gene

Answer 48

FTLD-TDP | -also assoc w ALS

Question 49

MYC amplification and isochromosome 17 (i17q)

Answer 49

Group 3 Medulloblastoma | -Mutation in i17q makes a medulloblastoma more resistant to chemo &worse prognosis

Question 50

defects in sonic hedgehog | -May have MYCN amplification

Answer 50

SHH type medullobalstoma

Question 51

X linked rec mutation in the ATP binding cassette transporter family of proteins (ABCD1) that transports molecules into the peroxisome.

Answer 51

Adrenoleukodystrophy