Tags

Type your tag names separated by a space and hit enter

The landscape of the mesenchymal signature in brain tumours.
Brain 2019; 142(4):847-866B

Abstract

The complexity of glioblastoma multiforme, the most common and lethal variant of gliomas, is reflected by cellular and molecular heterogeneity at both the inter- and intra-tumoural levels. Molecular subtyping has arisen in the past two decades as a promising strategy to give better predictions of glioblastoma multiforme evolution, common disease pathways, and rational treatment options. The Cancer Genome Atlas network initially identified four molecular subtypes of glioblastoma multiforme: proneural, neural, mesenchymal and classical. However, further studies, also investigated glioma stem cells, have only identified two to three subtypes: proneural, mesenchymal and classical. The proneural-mesenchymal transition upon tumour recurrence has been suggested as a mechanism of tumour resistance to radiation and chemotherapy treatment. Glioblastoma multiforme patients with the mesenchymal subtype tend to survive shorter than other subtypes when analysis is restricted to samples with low transcriptional heterogeneity. Although the mesenchymal signature in malignant glioma may seem at odds with the common idea of the ectodermal origin of neural-glial lineages, the presence of the mesenchymal signature in glioma is supported by several studies suggesting that it can result from: (i) intrinsic expression of tumour cells affected with accumulated genetic mutations and cell of origin; (ii) tumour micro-environments with recruited macrophages or microglia, mesenchymal stem cells or pericytes, and other progenitors; (iii) resistance to tumour treatment, including radiotherapy, antiangiogenic therapy and possibly chemotherapy. Genetic abnormalities, mainly NF1 mutations, together with NF-κB transcriptional programs, are the main driver of acquiring mesenchymal-signature. This signature is far from being simply tissue artefacts, as it has been identified in single cell glioma, circulating tumour cells, and glioma stem cells that are released from the tumour micro-environment. All these together suggest that the mesenchymal signature in glioblastoma multiforme is induced and sustained via cell intrinsic mechanisms and tumour micro-environment factors. Although patients with the mesenchymal subtype tend to have poorer prognosis, they may have favourable response to immunotherapy and intensive radio- and chemotherapy.

Authors+Show Affiliations

Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Stockholm, Sweden. Duke Preclinical Translational Unit, Duke University Medical Center, Durham, North Carolina.Unit of Molecular Neuro-Oncology, Neurological Institute C. Besta, Milan, Italy.Duke Preclinical Translational Unit, Duke University Medical Center, Durham, North Carolina.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30946477

Citation

Behnan, Jinan, et al. "The Landscape of the Mesenchymal Signature in Brain Tumours." Brain : a Journal of Neurology, vol. 142, no. 4, 2019, pp. 847-866.
Behnan J, Finocchiaro G, Hanna G. The landscape of the mesenchymal signature in brain tumours. Brain. 2019;142(4):847-866.
Behnan, J., Finocchiaro, G., & Hanna, G. (2019). The landscape of the mesenchymal signature in brain tumours. Brain : a Journal of Neurology, 142(4), pp. 847-866. doi:10.1093/brain/awz044.
Behnan J, Finocchiaro G, Hanna G. The Landscape of the Mesenchymal Signature in Brain Tumours. Brain. 2019 Apr 1;142(4):847-866. PubMed PMID: 30946477.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The landscape of the mesenchymal signature in brain tumours. AU - Behnan,Jinan, AU - Finocchiaro,Gaetano, AU - Hanna,Gabi, PY - 2018/09/19/received PY - 2019/01/07/revised PY - 2019/01/09/accepted PY - 2019/4/5/entrez PY - 2019/4/5/pubmed PY - 2019/4/5/medline KW - glioma KW - mesenchymal subtype KW - proneural-mesenchymal transition KW - subtype origin KW - tumor microenvironment SP - 847 EP - 866 JF - Brain : a journal of neurology JO - Brain VL - 142 IS - 4 N2 - The complexity of glioblastoma multiforme, the most common and lethal variant of gliomas, is reflected by cellular and molecular heterogeneity at both the inter- and intra-tumoural levels. Molecular subtyping has arisen in the past two decades as a promising strategy to give better predictions of glioblastoma multiforme evolution, common disease pathways, and rational treatment options. The Cancer Genome Atlas network initially identified four molecular subtypes of glioblastoma multiforme: proneural, neural, mesenchymal and classical. However, further studies, also investigated glioma stem cells, have only identified two to three subtypes: proneural, mesenchymal and classical. The proneural-mesenchymal transition upon tumour recurrence has been suggested as a mechanism of tumour resistance to radiation and chemotherapy treatment. Glioblastoma multiforme patients with the mesenchymal subtype tend to survive shorter than other subtypes when analysis is restricted to samples with low transcriptional heterogeneity. Although the mesenchymal signature in malignant glioma may seem at odds with the common idea of the ectodermal origin of neural-glial lineages, the presence of the mesenchymal signature in glioma is supported by several studies suggesting that it can result from: (i) intrinsic expression of tumour cells affected with accumulated genetic mutations and cell of origin; (ii) tumour micro-environments with recruited macrophages or microglia, mesenchymal stem cells or pericytes, and other progenitors; (iii) resistance to tumour treatment, including radiotherapy, antiangiogenic therapy and possibly chemotherapy. Genetic abnormalities, mainly NF1 mutations, together with NF-κB transcriptional programs, are the main driver of acquiring mesenchymal-signature. This signature is far from being simply tissue artefacts, as it has been identified in single cell glioma, circulating tumour cells, and glioma stem cells that are released from the tumour micro-environment. All these together suggest that the mesenchymal signature in glioblastoma multiforme is induced and sustained via cell intrinsic mechanisms and tumour micro-environment factors. Although patients with the mesenchymal subtype tend to have poorer prognosis, they may have favourable response to immunotherapy and intensive radio- and chemotherapy. SN - 1460-2156 UR - https://www.unboundmedicine.com/medline/citation/30946477/The_landscape_of_the_mesenchymal_signature_in_brain_tumours_ L2 - https://academic.oup.com/brain/article-lookup/doi/10.1093/brain/awz044 DB - PRIME DP - Unbound Medicine ER -