Molecular markers

Question 1

What molecular signs make an astrocytoma grade 4?

Answer 1

• IDH mut AND
• loss of ATRX (ATRX mut) or p53 mutation AND
• CDKN2A/B deletion

Question 2

What is MGMT?

Answer 2

o6-metylguanihn-DNA-metyltransferase

Question 3

What happens with MGMT when its gene promotor is methylated?

Answer 3

? enligt marias text så stängs enzymets funktion av? men det borde betyda att enzymet ej produceras och därmed ej kan reparera DNA vilket gör cellen känslig för alkylerande cytostatika.

Question 4

Something is special about some spinal ependymoma and they even got their own name. What?

Answer 4

MYCN amplified.

Question 5

If a CDKN 2A/B homozygous deletion is found in an Astrocytoma IDH mutant. What WHO grade does the tumor have?

Answer 5

Grade 4.

Question 6

What is the definition of an oligodendroglioma in WHO CNS 4?

Answer 6

• 1p/19q codeletion
• IDH mutation
• astrocytic appearance

Question 7

How is Oligodendroglioma graded?

Answer 7

Based on proliferative activity. Although no reliable treshold values exists.

Question 8

Glioblastoma - by definition IDH wt; usually have grade 4 astrocytoma typical histological features like necrosis and microvascular proliferation. But rarely they do not look like grade 4 histologically. What molecular alterations can be looked for in these cases to strengthen diagnosis?

Answer 8

• EGFR amplification
• TERTp mut
• gain of CHr 7
• loss of Chr 10.

Question 9

So, A Diffuse glioma is deemed IDH R132H wt.
What more is needed for diagnosis Glioblastoma IDH wt CNS WHO grade 4?

Answer 9

One or more of the following:
* microvascular proliferation
* Necrosis
* TERTp mutation
* EGFR gene amplificantion
* +7/-10

Question 10

A diffuse glioma is IDH1 R132H mutant. It also possesses an ATRX mutation.
If it doesnt have any microvascular proliferation or necrosis, what tumor is it then and what might change that statement?

Answer 10

It is then an Astrocytoma IDH mutant CNS WHO grade 2/3.
This will change into WHO grade 4 if it is found to have a homozygous CDKN2A/B deletion.

Question 11

A diffuse glioma is IDH1 mutant. It also possesses a p53 mutation.
If it doesnt have any microvascular proliferation or necrosis, what tumor is it then and what might change that statement?

Answer 11

It is then an Astrocytoma IDH mutant CNS WHO grade 2/3.
This will change into WHO grade 4 if it is found to have a homozygous CDKN2A/B deletion.

Question 12

A diffuse glioma is IDH1 R132H mutant. It does not have any p53 or ATRX mutation.
Is something more needed for us to know what tumor this is?

Question 13

What molecular signs make an IDH mutant astrocytoma grade 4 if the tumor also have microvascular proliferation and/or necrosis?

Answer 13

An ATRX mutation or a p53 mutation.

Question 14

what alkylating cyt is used for methylated MGMT tumors?

Answer 14

Temozolomid.

Question 15

What dubbeldeletion is strongly connected to oligodendroglioma?

Answer 15

1p19q deletion.

Question 16

What clinical traits are 1p19q codeletion associated with?

Answer 16

better prognosis and better response to cyt treatment. (uns)

Question 17

What is IDH?

Answer 17

the enzyme isocitratedehydrogenas 1 and 2.

Question 18

Does it matter if a tumor has IDH mutations?

Answer 18

If there are no other molecular changes that influence the prognosis, IDH mutations are associated with better prognosis than the wild type. But it doesnt change any treatment choices.

Question 19

What difference does a CKN1A/B mutation make?

Answer 19

it makes a WHO grade 2 a grade 3/4 instead.

Question 20

What tumor is H3K27 mutations associated to?

Answer 20

(pediatric) diffuse midline glioma, H3K27. (WHO grade 4, more aggressive than H3G34)

Question 21

What tumor is H3, G34 mutation associated to?

Answer 21

(pediatric) diffuse hemispheric glioma, H3G34. (WHO grade 4)

Question 22

What is K-67?

Answer 22

A nuclear antigen that gives information of proliferation. Proliferation index is % positive cell nuclei in the tumor. High=aggressive

Question 23

What does a P53 mutation suggest?

Answer 23

An astrocytic tumor. ( in oposition to oligodendroglioma)

Question 24

When is IDHmutation analysis done?

Answer 24

In all astrocytoma and oligodendroglioma

Question 25

When is 1p/19q deletion tested?

Answer 25

In all IDH mutated glioma grade II and III w kept ATRX expression.

Question 26

When is ATRX immunohistochemistry done?

Answer 26

In all astrocytoma and oligodendroglioma, if nuclear ATRX is lost, it is NOT an oligodendroglioma.

Question 27

When is MGMT promotormetylation tested?

Answer 27

In all astrocytoma and oligodendroglioma

Question 28

When is H3K27M immunohistochemistry and/or molecular assay run?

Answer 28

In diffuse midline glioma

Question 29

When is EGFR amplification assays run?

Answer 29

In IDH wt glioma with grade II or III histology

Question 30

When is Chromosome 7/10 status controlled ?

Answer 30

In IDH wt glioma with grade II or III histology

Question 31

When is TERT promotor mutaion controlled?

Answer 31

In IDH wt glioma with grade II or III histology

Question 32

When is p53 mutation assay run?

Answer 32

All astrocytoma and oligodendroglioma

Question 33

When is Ki-67 assay run?

Answer 33

In all astrocytoma and oligodendroglioma

Question 34

When is Ki-67 assay run?

Answer 34

In all astrocytoma and oligodendroglioma

Question 35

Loss of ———–expression is a strong indication of a astrocytoma and not a oligodendroglioma.

Answer 35

ATRX

Question 36

Mutation of ———is a strong indication of Astrocytoma and not Oligodendroglioma

Answer 36

p53

Question 37

What alteration warants a astrocytoma IDH mutant to go from grade 2/3 to grade 4 independent of microvascular proliferations and necrosis?

Answer 37

Homozygous CDKN2A/B