Glioblastoma multiforme classification: Difference between revisions
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==Overview== | ==Overview== | ||
Glioblastoma multiforme may be classified into several subtypes based on the origin (primary and secondary) and molecular alterations (classic, proneural, mesenchymal, and neural). | Glioblastoma multiforme may be classified into several subtypes based on the origin (primary and secondary) and molecular alterations (classic, proneural, mesenchymal, and neural).<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== | ||
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* Secondary GBM has increased signaling through PDGF-A 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. | * 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=== | ===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== | ||
Revision as of 18:27, 19 February 2019
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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).[1]
Classification
Based on the origin
Glioblastoma multiforme may be classified according to the origin into two subtypes: Primary and secondary.[2]
| Subtype of Glioblastoma multiforme | Characteristic features |
|---|---|
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- 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.
- ↑ Classification of Glioblastoma multiforme. Dr Dylan Kurda and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/Glioblastoma