1. Molecular markers related to patient outcome in patients with IDH-mutant astrocytomas grade 2 to 4: A systematic review.
- Author
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Tesileanu CMS, Vallentgoed WR, French PJ, and van den Bent MJ
- Subjects
- Biomarkers, Tumor genetics, DNA, DNA-Binding Proteins genetics, Homozygote, Humans, Isocitrate Dehydrogenase genetics, MutS Homolog 2 Protein genetics, Mutation, Phosphatidylinositol 3-Kinases genetics, Sequence Deletion, TOR Serine-Threonine Kinases genetics, Ubiquitin-Protein Ligases genetics, Astrocytoma genetics, Brain Neoplasms, Lymphoma, Follicular
- Abstract
Background: Grading and classification of IDH-mutant astrocytomas has shifted from solely histology towards histology combined with molecular diagnostics. In this systematic review, we give an overview of all currently known clinically relevant molecular markers within IDH-mutant astrocytomas grade 2 to 4., Methods: A literature search was performed in five electronic databases for English original papers on patient outcome with respect to a molecular marker as determined by DNA/RNA sequencing, micro-arrays, or DNA methylation profiling in IDH-mutant astrocytomas grade 2 to 4. Papers were included if molecular diagnostics were performed on tumour tissue of at least 15 IDH-mutant astrocytoma patients, and if the investigated molecular markers were not limited to the diagnostic markers MGMT, ATRX, TERT, and/or TP53., Results: The literature search identified 4508 unique articles, published between August 2012 and December 2021, of which ultimately 44 articles were included. Numerous molecular markers from these papers were significantly correlated to patient outcome. The associations between patient outcome and non-canonical IDH mutations, PI3K mutations, high expression of MSH2, high expression of RAD18, homozygous deletion of CDKN2A/B, amplification of PDGFRA, copy number neutral loss of chromosomal arm 17p, loss of chromosomal arm 19q, the G-CIMP-low DNA methylation cluster, high total CNV, and high tumour mutation burden were confirmed in multiple studies., Conclusions: Multiple genetic and epigenetic markers are associated with survival in IDH-mutant astrocytoma patients. Commonly affected are the RB signalling pathway, the RTK-PI3K-mTOR signalling pathway, genomic stability markers, and (epigenetic) gene regulation., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MJvdB reports grants from Dutch Cancer Foundation, grants from Brain Tumor Charity, grants from Strijd van Salland, grants from MSD formerly Schering Plough, during the conduct of the study; personal fees from Carthera, personal fees from Nerviano, personal fees from Bayer, personal fees from Celgene, personal fees from Agios, personal fees from Abbvie, personal fees from Karyopharm, personal fees from Boston Pharmaceuticals, personal fees from Genenta, outside the submitted work. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2022
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