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The Role of Next Generation Sequencing in Diagnosis of Brain Tumors: a Review Study

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The Role of Next Generation Sequencing in Diagnosis of Brain Tumors: a Review Study ArchiveArch Neurosci of .SID 2020 January; 7(1):e68874. doi: 10.5812/ans.68874. Published online 2019 November 11. Review Article The Role of Next Generation Sequencing in Diagnosis of Brain Tumors: A Review Study Sadegh Shirian 1, 2, Yahya Daneshbod 3, Saranaz Jangjoo 4, Amir Ghaemi 5, Arash Goodarzi 6, Maryam Ghavideldarestani 7, Ahmad Emadi 1, Arman Ai 8, Akbar Ahmadi 9, * and Jafar Ai 9, ** 1Department of Pathology, School of Veterinary Medicine, Shahrekord University, Shahrekord, Iran 2Shiraz Molecular Pathology Research Center, Dr Daneshbod Path Lab, Shiraz, Iran 3Department of Pathology and Laboratory Medicine, Loma Linda University, California, United States 4School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran 5Department of Virology, Pasteur Institute of Iran, Tehran, Iran 6Department of Tissue Engineering, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran 7Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran 8School of Medicine, Tehran University of Medical Sciences, Tehran, Iran 9Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran *Corresponding author: Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. Email: [email protected] **Corresponding author: Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. Email: [email protected] Received 2018 March 23; Revised 2019 July 03; Accepted 2019 July 31. Abstract Since the number of prognostic and predictive neuro-oncologic genetic markers is steadily increasing, a comprehensive analysis of the molecular techniques used to examine neuro-oncology samples is vastly required. Molecular analysis and profiling of brain ma- lignancies result in improved diagnostic accuracy, target identification, and predictive prognosis. Application of high-throughput molecular approaches, such as next generation sequencing (NGS), to analyze brain tumors has provided a large amount of molecu- lar information. In the clinical practice, the application of NGS has been increased, which has consequently improved the treatment option for brain cancer as well as other types of malignancies. Target therapy has recently become one of the most promising treat- ment options for various tumors, especially brain tumors. In this review, we provided and summarized high-throughput genomic studies, such as NGS technique, that could independently identify the integrated management and diagnosis of primary human brain tumors across a variety of entities with pathognomonic genetic alterations. Keywords: Next-Generation Sequencing, Brain Tumors, Target Identification, Genetic Markers 1. Context controls are necessary for preventing tumor malignancy (3). Since the number of prognostic and predictive neuro- According to the 3rd edition of the International Clas- oncologic genetic markers is steadily increasing, compre- sification of Diseases for Oncology, tumors of the central hensive analyses of the molecular techniques used to ex- nervous system (CNS) are those affecting the spinal cord amine neuro-oncology samples are vastly required for the and brain, including the pituitary gland, meninges, pineal evaluation of brain tumor specimens in a modern pathol- gland, and nerves (1). Brain tumors have been traditionally ogy setting. Molecular analysis and profiling of brain can- classified based on the microscopic investigation of hema- cers lead to improved diagnostic accuracy, target identi- toxylin and eosin- (H & E) stained tissue sections. The in- fication and predictive prognosis (4). The recent devel- creased comprehensive knowledge in relevant genetic al- opment of NGS technology and other complementary ge- terations and mutations with clinical outcomes resulted nomic platforms have transformed our capacity to investi- in the incorporation of molecular signatures as a part of gate the molecular landscapes of human cancers, includ- the diagnosis, management, and treatment of CNS ma- ing brain tumors (5). In this review, we summarized and lignancies (2). Various brain cancer susceptibility genes analyzed the results of high-throughput genomic studies, are involved in DNA damage response, which strongly in- such as NGS, in order to diagnose various types of brain tu- dicates that critical DNA repair pathways and checkpoint Copyright © 2019, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original workwww.SID.ir is properly cited. Archive of SID Shirian S et al. mors. ing optic glioma, cerebellar astrocytoma, and infundibu- loma due to their certain anatomic sites and the distinct predilection in young patients (14). Considering the dif- 2. Gliomas ficulty in diagnosing PA using anaplastic features that are exclusively based on morphology, applying the rele- Diffuse gliomas (DGs), the most common primary ma- vant molecular biomarkers to diagnose the presence of lignancy of the CNS, generally affect the cerebral hemi- mitogen-activating protein kinase (MAPK) pathway alter- spheres of adults. According to the World Health Organiza- ations are necessary (15). The results of whole genome se- tion (WHO) classification of the CNS tumors, lower-grade quencing have shown that single alterations of the MAPK gliomas or grades I and II DGs are oligodendrogliomas, pathway are solely detected in almost all PA cases, indicat- astrocytomas, and oligoastrocytomathat the latest is a ing that PA represents a one-pathway disease (14). Activa- less well-defined type of oligodendroglial (OA) (6). It has tion of MAPK signaling through various described muta- been reported that molecular landscape, such as 1p/19q co- tions or alterations, the commonest tandem duplication deletion status, is a better predictor of clinical outcome is located at 7q34 that leads to KIAA1459-BRAF fusion, is than that of the histologic distinction between oligoden- present in most of the PA cases. Therefore, the identifica- droglioma and OA (7). Therefore, the WHO has recently up- tion of a known mutation/alteration is useful to support dated the CNS tumor classification (8). In fact, NGS is an the diagnosis of PA (16-18). To investigate the full range effective technique for the detection of a wide variety of of genetic alterations present in PA, the whole genome molecular alterations, which provides an efficient, attrac- sequencing of DNA obtained from blood has been per- tive, as well as a cost-effective unimodal molecular plat- formed. Jones et al. have identified KIAA1549:BRAF fusion form for the classification of lower-grade gliomas based variants, FAM131B:BRAF fusion, four BRAFV600E mutations, on the 2016 WHO CNS criteria (9, 10). The results of the and one BRAFins599T in pediatric brain tumors by NGS anal- sequencing of the samples obtained from patients with ysis (16). It has been also detected a new recurrent alter- lower-grade gliomas, which were organized by IDH1, IDH2, ation, namely mutation of two hotspot residues (N546 and and NGS-based 1p/19q co-deletion status, are shown in Fig- K656) in the kinase domain of FGFR1 that are occasionally ure 1(11). Carter et al. have used a single, targeted NGS observed in adult glioblastoma (GBM) (19). The NGS anal- panel to detect single-nucleotide variation and copy num- ysis has also demonstrated that GIT2-BRAF fusion is identi- ber variation in 50 patients with lower-grade gliomas, in- cal to that detected in other fusion alterations in PA. This cluding 36 oligoastrocytomas, 11 oligodendrogliomas, 2 as- fusion most likely acts as a tumor driver that activates the trocytomas, and 1 lower-grade gliomas. They have found MAPK signaling pathway (20). that NGS is superior to fluorescence in situ hybridization (FISH) and immunohistochemistry in the detection of seg- mental chromosomal mutation from whole-arm deletions 4. Glioblastoma (GB) in glioma tumors (11). Targeted NGS for mutations in TP53, ATRX, CIC, IDH1, IDH2, FUBP1, PI3KC, EGFR, H3F3A, TERT, BRAF, Glioblastoma multiforme (GBM) is an extremely malig- PTEN, and NOTCH genes and for copy number alterations nant CNS tumor. Mutation and alteration of the epider- of chromosomes 1p, 19q, 10q, and 7 has been also used to mal growth factor receptor (EGFR) have been frequently re- classify DG (12) . Indeed, DGs could be classified as type I ported in various human malignancies, such as GBM (21). (1p/19q codeletion, “oligodendroglioma”), type II (IDH mu- However, the presence of multiple types or heterogeneous tation, “astrocytoma”), type III (TERT mutation or 7+/10q mutations is one of the GBM hallmarks that leads to insuffi- and 1p/19q intact, “glioblastoma”), and childhood glioblas- cient single-agent activity over standard treatments in pa- toma (H3F3A mutation) (12). tients with GBM (22). Therefore, the determination of pre- dictive biomarkers can predict the fate of EGFR-targeted 3. Pilocytic Astrocytoma therapy that resulted in help to the patients with GBM and improved the treatment sensitivity. In addition, de- Pilocytic astrocytomas (PAs) are WHO grade I CNS tu- tailed
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