Molecular markers Flashcards
What molecular signs make an astrocytoma grade 4?
- IDH mut AND
- loss of ATRX (ATRX mut) or p53 mutation AND
- CDKN2A/B deletion
What is MGMT?
o6-metylguanihn-DNA-metyltransferase
What happens with MGMT when its gene promotor is methylated?
? 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.
Something is special about some spinal ependymoma and they even got their own name. What?
MYCN amplified.
If a CDKN 2A/B homozygous deletion is found in an Astrocytoma IDH mutant. What WHO grade does the tumor have?
Grade 4.
What is the definition of an oligodendroglioma in WHO CNS 4?
- 1p/19q codeletion
- IDH mutation
- astrocytic appearance
How is Oligodendroglioma graded?
Based on proliferative activity. Although no reliable treshold values exists.
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?
- EGFR amplification
- TERTp mut
- gain of CHr 7
- loss of Chr 10.
So, A Diffuse glioma is deemed IDH R132H wt.
What more is needed for diagnosis Glioblastoma IDH wt CNS WHO grade 4?
One or more of the following:
* microvascular proliferation
* Necrosis
* TERTp mutation
* EGFR gene amplificantion
* +7/-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?
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.
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?
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.
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?
What molecular signs make an IDH mutant astrocytoma grade 4 if the tumor also have microvascular proliferation and/or necrosis?
An ATRX mutation or a p53 mutation.
what alkylating cyt is used for methylated MGMT tumors?
Temozolomid.
What dubbeldeletion is strongly connected to oligodendroglioma?
1p19q deletion.
What clinical traits are 1p19q codeletion associated with?
better prognosis and better response to cyt treatment. (uns)
What is IDH?
the enzyme isocitratedehydrogenas 1 and 2.
Does it matter if a tumor has IDH mutations?
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.
What difference does a CKN1A/B mutation make?
it makes a WHO grade 2 a grade 3/4 instead.
What tumor is H3K27 mutations associated to?
(pediatric) diffuse midline glioma, H3K27. (WHO grade 4, more aggressive than H3G34)
What tumor is H3, G34 mutation associated to?
(pediatric) diffuse hemispheric glioma, H3G34. (WHO grade 4)
What is K-67?
A nuclear antigen that gives information of proliferation. Proliferation index is % positive cell nuclei in the tumor. High=aggressive
What does a P53 mutation suggest?
An astrocytic tumor. ( in oposition to oligodendroglioma)
When is IDHmutation analysis done?
In all astrocytoma and oligodendroglioma
When is 1p/19q deletion tested?
In all IDH mutated glioma grade II and III w kept ATRX expression.
When is ATRX immunohistochemistry done?
In all astrocytoma and oligodendroglioma, if nuclear ATRX is lost, it is NOT an oligodendroglioma.
When is MGMT promotormetylation tested?
In all astrocytoma and oligodendroglioma
When is H3K27M immunohistochemistry and/or molecular assay run?
In diffuse midline glioma
When is EGFR amplification assays run?
In IDH wt glioma with grade II or III histology
When is Chromosome 7/10 status controlled ?
In IDH wt glioma with grade II or III histology
When is TERT promotor mutaion controlled?
In IDH wt glioma with grade II or III histology
When is p53 mutation assay run?
All astrocytoma and oligodendroglioma
When is Ki-67 assay run?
In all astrocytoma and oligodendroglioma
When is Ki-67 assay run?
In all astrocytoma and oligodendroglioma
Loss of ———–expression is a strong indication of a astrocytoma and not a oligodendroglioma.
ATRX
Mutation of ———is a strong indication of Astrocytoma and not Oligodendroglioma
p53
What alteration warants a astrocytoma IDH mutant to go from grade 2/3 to grade 4 independent of microvascular proliferations and necrosis?
Homozygous CDKN2A/B
