Glioblastoma multiforme classification: Difference between revisions
Jump to navigation
Jump to search
Marjan Khan (talk | contribs) No edit summary |
|||
| (12 intermediate revisions by 2 users not shown) | |||
| Line 1: | Line 1: | ||
__NOTOC__ | __NOTOC__ | ||
{{Glioblastoma multiforme}} | {{Glioblastoma multiforme}} | ||
{{CMG}}{{AE}}{{ | {{CMG}}{{AE}}{{Marjan}} | ||
==Overview== | ==Overview== | ||
Glioblastoma may be classified into several subtypes based on the origin and molecular alterations. | Glioblastoma multiforme may be classified into several subtypes based on the origin (primary and secondary) and molecular alterations (classic, proneural, mesenchymal, and neural).The heterogeneity of GBM profiles leads to different treatment efficacy among patients. The therapy must be personalized to target each patient’s alterations in the molecular level. <ref name="pmid20129251">{{cite journal| author=Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD et al.| title=Integrated genomic analysis identifies clinically relevant subtypes of Glioblastoma multiforme characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. | journal=Cancer Cell | year= 2010 | volume= 17 | issue= 1 | pages= 98-110 | pmid=20129251 | doi=10.1016/j.ccr.2009.12.020 | pmc=PMC2818769 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20129251 }} </ref> | ||
==Classification== | ==Classification== | ||
{| style="border: 0px; font-size: 90%; margin: 3px; width: 600px" align=center | ===Based on the origin=== | ||
|valign=top| | Glioblastoma multiforme may be classified according to the origin into two subtypes: Primary and secondary. | ||
{| style="border: 0px; font-size: 90%; margin: 3px; width: 600px" align="center" | |||
| valign="top" | | |||
|+ | |+ | ||
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Subtype of | ! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Subtype of Glioblastoma multiforme}} | ||
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Characteristic features}} | ! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Characteristic features}} | ||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | ||
:Primary glioblastoma | :Primary glioblastoma multiforme | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
*De novo origin | *De novo origin | ||
| Line 23: | Line 25: | ||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" | | | style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" | | ||
:Secondary glioblastoma | :Secondary glioblastoma multiforme | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
*Arises from pre-existing lower grade gliomas | *Arises from pre-existing lower grade gliomas | ||
| Line 29: | Line 31: | ||
*Occurs in younger patients | *Occurs in younger patients | ||
|} | |} | ||
* Primary GBM is the most common form (about 95%) and arises typically de novo, within 3–6 months, in older patients. | |||
* Secondary GBM arises from prior low-grade astrocytomas (over 10–15 years) in younger patients. | |||
* Primary and secondary forms show some molecular differences. | |||
* The end result of both sub type is same since the same pathways are affected and respond similarly to current standard treatment. | |||
* Primary GBM often has amplified and mutated epidermal-growth factor receptor (EGFR) which encodes altered EGF receptor. | |||
* Secondary GBM has increased signaling through PDGF-A receptor. | |||
* Both types of mutations lead to increased tyrosine kinase receptor (TKR) activity and consequently to activation of RAS and PI3K pathways. | |||
* Primary and secondary GBM may be indistinguishable histologically but apparently differ in genetic and epigenetic profiles. | |||
===Based on the molecular alterations=== | |||
* the Cancer Genome Atlas (TCGA) divided GBM according to the molecular alterations into four subtypes:<ref name="pmid20129251">{{cite journal| author=Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD et al.| title=Integrated genomic analysis identifies clinically relevant subtypes of Glioblastoma multiforme characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. | journal=Cancer Cell | year= 2010 | volume= 17 | issue= 1 | pages= 98-110 | pmid=20129251 | doi=10.1016/j.ccr.2009.12.020 | pmc=PMC2818769 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20129251 }} </ref> | |||
#'''Classic''' | |||
#'''Proneural''' | |||
#'''Mesenchymal''' | |||
#'''Neural''' | |||
* Classical GBM is defined by aberrant EGFR amplification with astrocytic cell expression pattern and loss of chromosome 10. | |||
* The mesenchymal subtype is defined by NF1 and PTEN mutations, a mesenchymal expression profile and less EGFR amplification than in other GBM types. | |||
* The proneural subtype is characterized by PDGFRA focal amplification, TP53 and IDH1 mutations with an oligodenrocytic cell expression profile and younger presentation age. | |||
* The neural subtype is characterized by normal brain tissue gene expression wuth astrocytic and oligodendrocytic cell markers. | |||
* Most GBM tumors with IDH1 mutations have the proneural gene expression pattern but only 30% of preneural GBM has the IDH1 mutation. | |||
* IDH1 mutation is a reliable and definitive molecular diagnostic criterion of secondary GBM compared to clinical criteria. | |||
* The heterogeneity of GBM profiles leads to different treatment efficacy among patients. | |||
* The therapy must be personalized to target each patient’s alterations in the molecular level. | |||
==References== | ==References== | ||
Latest revision as of 18:31, 19 February 2019
|
Glioblastoma multiforme Microchapters |
|
Diagnosis |
|---|
|
Treatment |
|
Case Studies |
|
Glioblastoma multiforme classification On the Web |
|
American Roentgen Ray Society Images of Glioblastoma multiforme classification |
|
Risk calculators and risk factors for Glioblastoma multiforme classification |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Marjan Khan M.B.B.S.[2]
Overview
Glioblastoma multiforme may be classified into several subtypes based on the origin (primary and secondary) and molecular alterations (classic, proneural, mesenchymal, and neural).The heterogeneity of GBM profiles leads to different treatment efficacy among patients. The therapy must be personalized to target each patient’s alterations in the molecular level. [1]
Classification
Based on the origin
Glioblastoma multiforme may be classified according to the origin into two subtypes: Primary and secondary.
| Subtype of Glioblastoma multiforme | Characteristic features |
|---|---|
|
|
|
|
- Primary GBM is the most common form (about 95%) and arises typically de novo, within 3–6 months, in older patients.
- Secondary GBM arises from prior low-grade astrocytomas (over 10–15 years) in younger patients.
- Primary and secondary forms show some molecular differences.
- The end result of both sub type is same since the same pathways are affected and respond similarly to current standard treatment.
- Primary GBM often has amplified and mutated epidermal-growth factor receptor (EGFR) which encodes altered EGF receptor.
- Secondary GBM has increased signaling through PDGF-A receptor.
- Both types of mutations lead to increased tyrosine kinase receptor (TKR) activity and consequently to activation of RAS and PI3K pathways.
- Primary and secondary GBM may be indistinguishable histologically but apparently differ in genetic and epigenetic profiles.
Based on the molecular alterations
- the Cancer Genome Atlas (TCGA) divided GBM according to the molecular alterations into four subtypes:[1]
- Classic
- Proneural
- Mesenchymal
- Neural
- Classical GBM is defined by aberrant EGFR amplification with astrocytic cell expression pattern and loss of chromosome 10.
- The mesenchymal subtype is defined by NF1 and PTEN mutations, a mesenchymal expression profile and less EGFR amplification than in other GBM types.
- The proneural subtype is characterized by PDGFRA focal amplification, TP53 and IDH1 mutations with an oligodenrocytic cell expression profile and younger presentation age.
- The neural subtype is characterized by normal brain tissue gene expression wuth astrocytic and oligodendrocytic cell markers.
- Most GBM tumors with IDH1 mutations have the proneural gene expression pattern but only 30% of preneural GBM has the IDH1 mutation.
- IDH1 mutation is a reliable and definitive molecular diagnostic criterion of secondary GBM compared to clinical criteria.
- The heterogeneity of GBM profiles leads to different treatment efficacy among patients.
- The therapy must be personalized to target each patient’s alterations in the molecular level.
References
- ↑ 1.0 1.1 Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD; et al. (2010). "Integrated genomic analysis identifies clinically relevant subtypes of Glioblastoma multiforme characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1". Cancer Cell. 17 (1): 98–110. doi:10.1016/j.ccr.2009.12.020. PMC 2818769. PMID 20129251.