Journal Club

Question 1

What are Cranial and Spinal meningiomas usually associated with

Answer 1

NF2 - a tumour suppressor syndrome and SWI/SNF chromatin-remodeling complex subunits

Question 2

familial meningioma

Answer 2

more likely to occur in family members than chance

- there is a subset of individuals with familial meningiomas not associated with NF2 mutations

Question 3

what percent of exons were sequenced in methods

Answer 3

73-77%

Question 4

function of the SMARCE1 gene

Answer 4

induces apoptosis

Question 5

what did they focus on when they realized there was no NF2 mutation

Answer 5

SWI/SNF chromatin remodelling complex

Question 6

what was the mutation in the SMARCE1 genome in family one

Answer 6

-on the first base of exon 9 there was a mutation, stop codon was introduced resulting in mRNA decay

Question 7

loss of heterozygosity

Answer 7

loss of the wild-type allele

Question 8

what was the mutation in the SMARCE1 genome in family two

Answer 8

• exon 5 also had a premature stop codon (in-frame deletion of exon 5)
• alternatively spliced the mRNA transcripts

Question 9

Family three SMARCE1 mutation

Answer 9

• no SMARCE1 mutation identified in 34 cranial meningioma

- mutation specific to spinal tumours

Question 10

Immunohistochemistry

Answer 10

-antibody attached to colour producing enzyme that binds to proteins

Question 11

what does the loss of heterozygosity suggest

Answer 11

that it functions as a tumour suppressor to in induce apoptosis

Question 12

define meningioma

Answer 12

benign tumour that arises from meninges of the brain and spinal cord called the arachnoid

Question 13

somatic mutations

Answer 13

non-inheritable mutation occurring in a somatic cell

Question 14

germ line mutation

Answer 14

forms the reproductive cells, inheritable, embryonic cell lineage

Question 15

sporadic

Answer 15

occurs in single and scattered cases

Question 16

familial

Answer 16

transmitted and expressed by members of a family

Question 17

is there clinical symptoms of NF2

Answer 17

no

Question 18

the chromatin-remodelling complex in this paper

Answer 18

• 2 Mda multi-subunits (multi-protein)
• regulates gene transcription
• alters the chromosome structure by nucleosome remodelling

Question 19

exome sequencing

Answer 19

• selective sequencing of the coding regions of the genome
• exons represent regions of the gene that turn into protein
• used to screen for genomic mutations

Question 20

family 2 mutation (again)

Answer 20

• insertion of the first 18 bases of intron 5 which introduced an in-frame premature stop codon after the 3rd codon
• in-frame deletion of exon 5 which contains an important functional domain

Question 21

what colour is cranial stain

Answer 21

pink (eosin)

Question 22

what colour is spinal stain

Answer 22

blue

Question 23

what is loss of heterozygosity

Answer 23

• when there is a mutation in a wild-type allele
• individuals normal cells are heterozygous (no disease)
• this mutation leads to cancerous phenotype

Question 24

What family observed a loss of heterozygosity

Answer 24

family 3

Question 25

What syndrome also has mutation in the SWI/SNF complex

Answer 25

coffin siris syndrom. CNS tumours are rarely found here

Question 26

does the loss of function mutations in SMARCE1 predispose individuals to specific disease phenotype

Answer 26

likely specific to familial SPINAL meningiomas

–>CNS tumours rarely found in SMARCE1 mutation

Question 27

3 steps of apoptosis

Answer 27

1. Nuclear DNA fragmented
2. internal cellular structures are disrupted
3. cell dissolves into small spherical strictures: apoptotic bodies

Question 28

tumour suppressor genes

Answer 28

-genes who’s products normally regulate the cell-cycle checkpoints, initiate apoptosis

Question 29

what does the mutation in tumour suppressor genes do

Answer 29

-lead to the accumulation of more mutations and the development of cancer

Question 30

info about the SMARCE1 gene

Answer 30

• 11 exons
• encodes 57 kDa subunit of the SWI/SNF complex
• only in higher eukaryotes
• isoforms lacking 3 and 4 are confined to neurons (alternative splicing)

Question 31

what does SMARCE1 protein do

Answer 31

-induces apoptosis by stimulating the expression of a tumour suppressor gene

Question 32

SMARCE1 in spinal meningioma

Answer 32

• loss of expression in spinal meningioma tumours
• cells are not triggered to undergo apoptosis
• likely a specific function in this meningioma subtype