A Targeted Next-Generation Sequencing Panel to Genotype Gliomas
Abstract
:1. Introduction
2. Materials and Methods
2.1. Sample Collection
2.2. DNA Extraction and Dosage
2.3. NGS Panel Design
2.4. Library Preparation
2.5. Chip Loading and Sequencing
2.6. Analytical Specificity and Sensitivity
2.7. Variant Calling and Prioritization
3. Results
3.1. Study Population
3.2. Target Gene Coverage
3.3. Variant Interpretation
3.4. Assessment of Sensitivity and Specificity
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
AF | Allelic frequencies |
ALT | Alternative lengthening of telomeres |
AML | Acute myeloid leukemia |
AMP–ASCO–CAP | Association for Molecular Pathology, AMP; American Society of Clinical Oncology, ASCO; and College of American Pathologists, CAP |
ATRX | α thalassemia/mental retardation syndrome X-linked gene |
BRAF | B-Raf proto-oncogene |
cIMPACT | Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy |
CNAs | Copy number alterations |
COSMIC | Catalogue OF Somatic Mutations In Cancer |
EGFR | Epidermal growth factor receptor |
GBM | Glioblastoma |
GDC | Genomic Data Commons |
GOF | Gain of function |
IARC | International Agency for Research on Cancer |
IDH | Isocitrate dehydrogenase |
LOH | Loss of heterozygosity |
MGMT | O6-methylguanine (O6-MeG)-DNA methyltransferase |
NGS | Next generation sequencing |
OS | Overall survival |
PDGFR | Platelet-derived growth factor receptor |
PTEN | Phosphatase and tensin Homolog |
SNVs | Single nucleotide variants |
TCGA | Cancer Genome Atlas |
TERT | Telomerase reverse transcriptase |
TMZ | Temozolomide |
TP53 | Tumor protein P53 |
WHO | World Health Organization |
References
- Yoon, N.; Kim, H.S.; Lee, J.W.; Lee, E.J.; Maeng, L.S.; Yoon, W.S. Targeted Genomic Sequencing Reveals Different Evolutionary Patterns Between Locally and Distally Recurrent Glioblastomas. Cancer Genom. Proteom. 2020, 17, 803–812. [Google Scholar] [CrossRef] [PubMed]
- Sakthikumar, S.; Roy, A.; Haseeb, L.; Pettersson, M.E.; Sundstrom, E.; Marinescu, V.D.; Lindblad-Toh, K.; Forsberg-Nilsson, K. Whole-genome sequencing of glioblastoma reveals enrichment of non-coding constraint mutations in known and novel genes. Genome Biol. 2020, 21, 127. [Google Scholar] [CrossRef] [PubMed]
- Pesenti, C.; Navone, S.E.; Guarnaccia, L.; Terrasi, A.; Costanza, J.; Silipigni, R.; Guarneri, S.; Fusco, N.; Fontana, L.; Locatelli, M.; et al. The Genetic Landscape of Human Glioblastoma and Matched Primary Cancer Stem Cells Reveals Intratumour Similarity and Intertumour Heterogeneity. Stem Cells Int. 2019, 2019, 2617030. [Google Scholar] [CrossRef]
- Ohgaki, H.; Kleihues, P. The definition of primary and secondary glioblastoma. Clin. Cancer Res. 2013, 19, 764–772. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Campanella, R.; Guarnaccia, L.; Caroli, M.; Zarino, B.; Carrabba, G.; La Verde, N.; Gaudino, C.; Rampini, A.; Luzzi, S.; Riboni, L.; et al. Personalized and translational approach for malignant brain tumors in the era of precision medicine: The strategic contribution of an experienced neurosurgery laboratory in a modern neurosurgery and neuro-oncology department. J. Neurol. Sci. 2020, 417, 117083. [Google Scholar] [CrossRef] [PubMed]
- Verhaak, R.G.; Hoadley, K.A.; Purdom, E.; Wang, V.; Qi, Y.; Wilkerson, M.D.; Miller, C.R.; Ding, L.; Golub, T.; Mesirov, J.P.; et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 2010, 17, 98–110. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Behnan, J.; Finocchiaro, G.; Hanna, G. The landscape of the mesenchymal signature in brain tumours. Brain 2019, 142, 847–866. [Google Scholar] [CrossRef] [Green Version]
- Cohen, A.L.; Holmen, S.L.; Colman, H. IDH1 and IDH2 mutations in gliomas. Curr. Neurol. Neurosci. Rep. 2013, 13, 345. [Google Scholar] [CrossRef] [Green Version]
- Woo, H.Y.; Na, K.; Yoo, J.; Chang, J.H.; Park, Y.N.; Shim, H.S.; Kim, S.H. Glioblastomas harboring gene fusions detected by next-generation sequencing. Brain Tumor Pathol. 2020, 37, 136–144. [Google Scholar] [CrossRef]
- Ceccarelli, M.; D’Andrea, G.; Micheli, L.; Gentile, G.; Cavallaro, S.; Merlino, G.; Papoff, G.; Tirone, F. Tumor Growth in the High Frequency Medulloblastoma Mouse Model Ptch1(+/−)/Tis21(KO) Has a Specific Activation Signature of the PI3K/AKT/mTOR Pathway and Is Counteracted by the PI3K Inhibitor MEN1611. Front. Oncol. 2021, 11, 692053. [Google Scholar] [CrossRef]
- Blomquist, M.R.; Ensign, S.F.; D’Angelo, F.; Phillips, J.J.; Ceccarelli, M.; Peng, S.; Halperin, R.F.; Caruso, F.P.; Garofano, L.; Byron, S.A.; et al. Temporospatial genomic profiling in glioblastoma identifies commonly altered core pathways underlying tumor progression. Neurooncol. Adv. 2020, 2, vdaa078. [Google Scholar] [CrossRef] [PubMed]
- Louis, D.N.; Perry, A.; Wesseling, P.; Brat, D.J.; Cree, I.A.; Figarella-Branger, D.; Hawkins, C.; Ng, H.K.; Pfister, S.M.; Reifenberger, G.; et al. The 2021 WHO Classification of Tumors of the Central Nervous System: A summary. Neuro Oncol. 2021, 23, 1231–1251. [Google Scholar] [CrossRef] [PubMed]
- Brennan, C.W.; Verhaak, R.G.; McKenna, A.; Campos, B.; Noushmehr, H.; Salama, S.R.; Zheng, S.; Chakravarty, D.; Sanborn, J.Z.; Berman, S.H.; et al. The somatic genomic landscape of glioblastoma. Cell 2013, 155, 462–477. [Google Scholar] [CrossRef] [PubMed]
- Gadji, M.; Fortin, D.; Tsanaclis, A.M.; Drouin, R. Is the 1p/19q deletion a diagnostic marker of oligodendrogliomas? Cancer Genet. Cytogenet. 2009, 194, 12–22. [Google Scholar] [CrossRef] [PubMed]
- Lin, Y.; Xing, Z.; She, D.; Yang, X.; Zheng, Y.; Xiao, Z.; Wang, X.; Cao, D. IDH mutant and 1p/19q co-deleted oligodendrogliomas: Tumor grade stratification using diffusion-, susceptibility-, and perfusion-weighted MRI. Neuroradiology 2017, 59, 555–562. [Google Scholar] [CrossRef]
- Stichel, D.; Ebrahimi, A.; Reuss, D.; Schrimpf, D.; Ono, T.; Shirahata, M.; Reifenberger, G.; Weller, M.; Hanggi, D.; Wick, W.; et al. Distribution of EGFR amplification, combined chromosome 7 gain and chromosome 10 loss, and TERT promoter mutation in brain tumors and their potential for the reclassification of IDHwt astrocytoma to glioblastoma. Acta Neuropathol. 2018, 136, 793–803. [Google Scholar] [CrossRef] [Green Version]
- Crespo, I.; Vital, A.L.; Nieto, A.B.; Rebelo, O.; Tao, H.; Lopes, M.C.; Oliveira, C.R.; French, P.J.; Orfao, A.; Tabernero, M.D. Detailed characterization of alterations of chromosomes 7, 9, and 10 in glioblastomas as assessed by single-nucleotide polymorphism arrays. J. Mol. Diagn. 2011, 13, 634–647. [Google Scholar] [CrossRef]
- Tan, J.Y.; Wijesinghe, I.V.S.; Alfarizal Kamarudin, M.N.; Parhar, I. Paediatric Gliomas: BRAF and Histone H3 as Biomarkers, Therapy and Perspective of Liquid Biopsies. Cancers 2021, 13, 607. [Google Scholar] [CrossRef]
- Villa, C.; Miquel, C.; Mosses, D.; Bernier, M.; Di Stefano, A.L. The 2016 World Health Organization classification of tumours of the central nervous system. Presse Med. 2018, 47, e187–e200. [Google Scholar] [CrossRef]
- Komori, T. Grading of adult diffuse gliomas according to the 2021 WHO Classification of Tumors of the Central Nervous System. Lab. Investig. 2021, 102, 126–133. [Google Scholar] [CrossRef]
- Zhang, P.; Xia, Q.; Liu, L.; Li, S.; Dong, L. Current Opinion on Molecular Characterization for GBM Classification in Guiding Clinical Diagnosis, Prognosis, and Therapy. Front. Mol. Biosci. 2020, 7, 562798. [Google Scholar] [CrossRef] [PubMed]
- Theeler, B.J.; Gilbert, M.R. Advances in the treatment of newly diagnosed glioblastoma. BMC Med. 2015, 13, 293. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yang, J.; Wang, L.; Xu, Z.; Wu, L.; Liu, B.; Wang, J.; Tian, D.; Xiong, X.; Chen, Q. Integrated Analysis to Evaluate the Prognostic Value of Signature mRNAs in Glioblastoma Multiforme. Front. Genet. 2020, 11, 253. [Google Scholar] [CrossRef] [PubMed]
- Weller, M.; van den Bent, M.; Preusser, M.; Le Rhun, E.; Tonn, J.C.; Minniti, G.; Bendszus, M.; Balana, C.; Chinot, O.; Dirven, L.; et al. EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood. Nat. Rev. Clin. Oncol. 2021, 18, 170–186. [Google Scholar] [CrossRef]
- Guan, Y.F.; Li, G.R.; Wang, R.J.; Yi, Y.T.; Yang, L.; Jiang, D.; Zhang, X.P.; Peng, Y. Application of next-generation sequencing in clinical oncology to advance personalized treatment of cancer. Chin. J. Cancer 2012, 31, 463–470. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lorenz, J.; Rothhammer-Hampl, T.; Zoubaa, S.; Bumes, E.; Pukrop, T.; Kolbl, O.; Corbacioglu, S.; Schmidt, N.O.; Proescholdt, M.; Hau, P.; et al. A comprehensive DNA panel next generation sequencing approach supporting diagnostics and therapy prediction in neurooncology. Acta Neuropathol. Commun. 2020, 8, 124. [Google Scholar] [CrossRef]
- Sahm, F.; Schrimpf, D.; Jones, D.T.; Meyer, J.; Kratz, A.; Reuss, D.; Capper, D.; Koelsche, C.; Korshunov, A.; Wiestler, B.; et al. Next-generation sequencing in routine brain tumor diagnostics enables an integrated diagnosis and identifies actionable targets. Acta Neuropathol. 2016, 131, 903–910. [Google Scholar] [CrossRef]
- Wesseling, P.; Capper, D. WHO 2016 Classification of gliomas. Neuropathol. Appl. Neurobiol. 2018, 44, 139–150. [Google Scholar] [CrossRef]
- Stupp, R.; Taillibert, S.; Kanner, A.A.; Kesari, S.; Steinberg, D.M.; Toms, S.A.; Taylor, L.P.; Lieberman, F.; Silvani, A.; Fink, K.L.; et al. Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial. JAMA 2015, 314, 2535–2543. [Google Scholar] [CrossRef]
- D’Haene, N.; Melendez, B.; Blanchard, O.; De Neve, N.; Lebrun, L.; Van Campenhout, C.; Salmon, I. Design and Validation of a Gene-Targeted, Next-Generation Sequencing Panel for Routine Diagnosis in Gliomas. Cancers 2019, 11, 773. [Google Scholar] [CrossRef] [Green Version]
- Trevethan, R. Sensitivity, Specificity, and Predictive Values: Foundations, Pliabilities, and Pitfalls in Research and Practice. Front. Public Health 2017, 5, 307. [Google Scholar] [CrossRef] [PubMed]
- Jennings, L.J.; Arcila, M.E.; Corless, C.; Kamel-Reid, S.; Lubin, I.M.; Pfeifer, J.; Temple-Smolkin, R.L.; Voelkerding, K.V.; Nikiforova, M.N. Guidelines for Validation of Next-Generation Sequencing-Based Oncology Panels: A Joint Consensus Recommendation of the Association for Molecular Pathology and College of American Pathologists. J. Mol. Diagn. 2017, 19, 341–365. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Singh, R.R. Next-Generation Sequencing in High-Sensitive Detection of Mutations in Tumors: Challenges, Advances, and Applications. J. Mol. Diagn. 2020, 22, 994–1007. [Google Scholar] [CrossRef] [PubMed]
- Dagogo-Jack, I.; Shaw, A.T. Tumour heterogeneity and resistance to cancer therapies. Nat. Rev. Clin. Oncol. 2018, 15, 81–94. [Google Scholar] [CrossRef] [PubMed]
- Dubbink, H.J.; Atmodimedjo, P.N.; van Marion, R.; Krol, N.M.G.; Riegman, P.H.J.; Kros, J.M.; van den Bent, M.J.; Dinjens, W.N.M. Diagnostic Detection of Allelic Losses and Imbalances by Next-Generation Sequencing: 1p/19q Co-Deletion Analysis of Gliomas. J. Mol. Diagn. 2016, 18, 775–786. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hatanpaa, K.J.; Burger, P.C.; Eshleman, J.R.; Murphy, K.M.; Berg, K.D. Molecular diagnosis of oligodendroglioma in paraffin sections. Lab. Investig. 2003, 83, 419–428. [Google Scholar] [CrossRef] [Green Version]
- Fontana, L.; Tabano, S.; Bonaparte, E.; Marfia, G.; Pesenti, C.; Falcone, R.; Augello, C.; Carlessi, N.; Silipigni, R.; Guerneri, S.; et al. MGMT-Methylated Alleles Are Distributed Heterogeneously Within Glioma Samples Irrespective of IDH Status and Chromosome 10q Deletion. J. Neuropathol. Exp. Neurol. 2016, 75, 791–800. [Google Scholar] [CrossRef] [Green Version]
- Zhang, D.; Xia, J. Somatic synonymous mutations in regulatory elements contribute to the genetic aetiology of melanoma. BMC Med. Genom. 2020, 13, 43. [Google Scholar] [CrossRef]
- Gotea, V.; Gartner, J.J.; Qutob, N.; Elnitski, L.; Samuels, Y. The functional relevance of somatic synonymous mutations in melanoma and other cancers. Pigment Cell Melanoma Res. 2015, 28, 673–684. [Google Scholar] [CrossRef] [Green Version]
- Qi, S.; Yu, L.; Li, H.; Ou, Y.; Qiu, X.; Ding, Y.; Han, H.; Zhang, X. Isocitrate dehydrogenase mutation is associated with tumor location and magnetic resonance imaging characteristics in astrocytic neoplasms. Oncol. Lett. 2014, 7, 1895–1902. [Google Scholar] [CrossRef] [Green Version]
- Reitman, Z.J.; Yan, H. Isocitrate dehydrogenase 1 and 2 mutations in cancer: Alterations at a crossroads of cellular metabolism. J. Natl. Cancer Inst. 2010, 102, 932–941. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Starkova, J.; Hermanova, I.; Hlozkova, K.; Hararova, A.; Trka, J. Altered Metabolism of Leukemic Cells: New Therapeutic Opportunity. Int. Rev. Cell Mol. Biol. 2018, 336, 93–147. [Google Scholar] [CrossRef] [PubMed]
- Berger, M.S.; Hervey-Jumper, S.; Wick, W. Astrocytic gliomas WHO grades II and III. Handb. Clin. Neurol. 2016, 134, 345–360. [Google Scholar] [CrossRef] [PubMed]
- Tommasini-Ghelfi, S.; Murnan, K.; Kouri, F.M.; Mahajan, A.S.; May, J.L.; Stegh, A.H. Cancer-associated mutation and beyond: The emerging biology of isocitrate dehydrogenases in human disease. Sci. Adv. 2019, 5, eaaw4543. [Google Scholar] [CrossRef] [Green Version]
- Yang, H.; Ye, D.; Guan, K.L.; Xiong, Y. IDH1 and IDH2 mutations in tumorigenesis: Mechanistic insights and clinical perspectives. Clin. Cancer Res. 2012, 18, 5562–5571. [Google Scholar] [CrossRef] [Green Version]
- Mu, L.; Xu, W.; Li, Q.; Ge, H.; Bao, H.; Xia, S.; Ji, J.; Jiang, J.; Song, Y.; Gao, Q. IDH1 R132H Mutation Is Accompanied with Malignant Progression of Paired Primary-Recurrent Astrocytic Tumours. J. Cancer 2017, 8, 2704–2712. [Google Scholar] [CrossRef] [Green Version]
- Guo, J.; Zhang, R.; Yang, Z.; Duan, Z.; Yin, D.; Zhou, Y. Biological Roles and Therapeutic Applications of IDH2 Mutations in Human Cancer. Front. Oncol. 2021, 11, 644857. [Google Scholar] [CrossRef]
- Lee, E.Q.; Kaley, T.J.; Duda, D.G.; Schiff, D.; Lassman, A.B.; Wong, E.T.; Mikkelsen, T.; Purow, B.W.; Muzikansky, A.; Ancukiewicz, M.; et al. A Multicenter, Phase II, Randomized, Noncomparative Clinical Trial of Radiation and Temozolomide with or without Vandetanib in Newly Diagnosed Glioblastoma Patients. Clin. Cancer Res. 2015, 21, 3610–3618. [Google Scholar] [CrossRef] [Green Version]
- DiNardo, C.D.; Stein, A.S.; Stein, E.M.; Fathi, A.T.; Frankfurt, O.; Schuh, A.C.; Dohner, H.; Martinelli, G.; Patel, P.A.; Raffoux, E.; et al. Mutant Isocitrate Dehydrogenase 1 Inhibitor Ivosidenib in Combination With Azacitidine for Newly Diagnosed Acute Myeloid Leukemia. J. Clin. Oncol. 2021, 39, 57–65. [Google Scholar] [CrossRef]
- Mellinghoff, I.K.; Ellingson, B.M.; Touat, M.; Maher, E.; De La Fuente, M.I.; Holdhoff, M.; Cote, G.M.; Burris, H.; Janku, F.; Young, R.J.; et al. Ivosidenib in Isocitrate Dehydrogenase 1-Mutated Advanced Glioma. J. Clin. Oncol. 2020, 38, 3398–3406. [Google Scholar] [CrossRef]
- Sigismund, S.; Avanzato, D.; Lanzetti, L. Emerging functions of the EGFR in cancer. Mol. Oncol. 2018, 12, 3–20. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Saadeh, F.S.; Mahfouz, R.; Assi, H.I. EGFR as a clinical marker in glioblastomas and other gliomas. Int. J. Biol. Markers 2018, 33, 22–32. [Google Scholar] [CrossRef] [Green Version]
- Pan, P.C.; Magge, R.S. Mechanisms of EGFR Resistance in Glioblastoma. Int. J. Mol. Sci. 2020, 21, 8471. [Google Scholar] [CrossRef] [PubMed]
- Makhlin, I.; Salinas, R.D.; Zhang, D.; Jacob, F.; Ming, G.L.; Song, H.; Saxena, D.; Dorsey, J.F.; Nasrallah, M.P.; Morrissette, J.J.; et al. Clinical activity of the EGFR tyrosine kinase inhibitor osimertinib in EGFR-mutant glioblastoma. CNS Oncol. 2019, 8, CNS43. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chagoya, G.; Kwatra, S.G.; Nanni, C.W.; Roberts, C.M.; Phillips, S.M.; Nullmeyergh, S.; Gilmore, S.P.; Spasojevic, I.; Corcoran, D.L.; Young, C.C.; et al. Efficacy of osimertinib against EGFRvIII+ glioblastoma. Oncotarget 2020, 11, 2074–2082. [Google Scholar] [CrossRef]
- Olympios, N.; Gilard, V.; Marguet, F.; Clatot, F.; Di Fiore, F.; Fontanilles, M. TERT Promoter Alterations in Glioblastoma: A Systematic Review. Cancers 2021, 13, 1147. [Google Scholar] [CrossRef]
- Vinagre, J.; Almeida, A.; Populo, H.; Batista, R.; Lyra, J.; Pinto, V.; Coelho, R.; Celestino, R.; Prazeres, H.; Lima, L.; et al. Frequency of TERT promoter mutations in human cancers. Nat. Commun. 2013, 4, 2185. [Google Scholar] [CrossRef] [Green Version]
- Jeong, D.E.; Woo, S.R.; Nam, H.; Nam, D.H.; Lee, J.H.; Joo, K.M. Preclinical and clinical implications of TERT promoter mutation in glioblastoma multiforme. Oncol. Lett. 2017, 14, 8213–8219. [Google Scholar] [CrossRef]
- Rachakonda, P.S.; Hosen, I.; de Verdier, P.J.; Fallah, M.; Heidenreich, B.; Ryk, C.; Wiklund, N.P.; Steineck, G.; Schadendorf, D.; Hemminki, K.; et al. TERT promoter mutations in bladder cancer affect patient survival and disease recurrence through modification by a common polymorphism. Proc. Natl. Acad. Sci. USA 2013, 110, 17426–17431. [Google Scholar] [CrossRef] [Green Version]
- Amen, A.M.; Fellmann, C.; Soczek, K.M.; Ren, S.M.; Lew, R.J.; Knott, G.J.; Park, J.E.; McKinney, A.M.; Mancini, A.; Doudna, J.A.; et al. Cancer-specific loss of TERT activation sensitizes glioblastoma to DNA damage. Proc. Natl. Acad. Sci. USA 2021, 118, e2008772118. [Google Scholar] [CrossRef]
- Zhang, Y.; Dube, C.; Gibert, M., Jr.; Cruickshanks, N.; Wang, B.; Coughlan, M.; Yang, Y.; Setiady, I.; Deveau, C.; Saoud, K.; et al. The p53 Pathway in Glioblastoma. Cancers 2018, 10, 297. [Google Scholar] [CrossRef] [Green Version]
- Hanel, W.; Marchenko, N.; Xu, S.; Yu, S.X.; Weng, W.; Moll, U. Two hot spot mutant p53 mouse models display differential gain of function in tumorigenesis. Cell Death Differ. 2013, 20, 898–909. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wong, P.; Verselis, S.J.; Garber, J.E.; Schneider, K.; DiGianni, L.; Stockwell, D.H.; Li, F.P.; Syngal, S. Prevalence of early onset colorectal cancer in 397 patients with classic Li-Fraumeni syndrome. Gastroenterology 2006, 130, 73–79. [Google Scholar] [CrossRef] [PubMed]
- Manoharan, V.; Karunanayake, E.H.; Tennekoon, K.H.; De Silva, S.; Imthikab, A.I.A.; De Silva, K.; Angunawela, P.; Vishwakula, S.; Lunec, J. Pattern of nucleotide variants of TP53 and their correlation with the expression of p53 and its downstream proteins in a Sri Lankan cohort of breast and colorectal cancer patients. BMC Cancer 2020, 20, 72. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- De Luca, C.; Race, V.; Keldermans, L.; Bauters, M.; Van Esch, H. Challenges in molecular diagnosis of X-linked Intellectual disability. Br. Med. Bull. 2020, 133, 36–48. [Google Scholar] [CrossRef] [PubMed]
- Nandakumar, P.; Mansouri, A.; Das, S. The Role of ATRX in Glioma Biology. Front. Oncol. 2017, 7, 236. [Google Scholar] [CrossRef] [PubMed]
- Haase, S.; Garcia-Fabiani, M.B.; Carney, S.; Altshuler, D.; Nunez, F.J.; Mendez, F.M.; Nunez, F.; Lowenstein, P.R.; Castro, M.G. Mutant ATRX: Uncovering a new therapeutic target for glioma. Expert Opin. Ther. Targets 2018, 22, 599–613. [Google Scholar] [CrossRef]
- Qin, T.; Mullan, B.; Ravindran, R.; Messinger, D.; Siada, R.; Cummings, J.R.; Harris, M.; Muruganand, A.; Pyaram, K.; Miklja, Z.; et al. ATRX loss in glioma results in dysregulation of cell-cycle phase transition and ATM inhibitor radio-sensitization. Cell Rep. 2022, 38, 110216. [Google Scholar] [CrossRef]
- Benitez, J.A.; Ma, J.; D’Antonio, M.; Boyer, A.; Camargo, M.F.; Zanca, C.; Kelly, S.; Khodadadi-Jamayran, A.; Jameson, N.M.; Andersen, M.; et al. PTEN regulates glioblastoma oncogenesis through chromatin-associated complexes of DAXX and histone H3.3. Nat. Commun. 2017, 8, 15223. [Google Scholar] [CrossRef]
- Han, F.; Hu, R.; Yang, H.; Liu, J.; Sui, J.; Xiang, X.; Wang, F.; Chu, L.; Song, S. PTEN gene mutations correlate to poor prognosis in glioma patients: A meta-analysis. Onco Targets Ther. 2016, 9, 3485–3492. [Google Scholar] [CrossRef] [Green Version]
- Ozawa, T.; Brennan, C.W.; Wang, L.; Squatrito, M.; Sasayama, T.; Nakada, M.; Huse, J.T.; Pedraza, A.; Utsuki, S.; Yasui, Y.; et al. PDGFRA gene rearrangements are frequent genetic events in PDGFRA-amplified glioblastomas. Genes Dev. 2010, 24, 2205–2218. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Alentorn, A.; Marie, Y.; Carpentier, C.; Boisselier, B.; Giry, M.; Labussiere, M.; Mokhtari, K.; Hoang-Xuan, K.; Sanson, M.; Delattre, J.Y.; et al. Prevalence, clinico-pathological value, and co-occurrence of PDGFRA abnormalities in diffuse gliomas. Neuro Oncol. 2012, 14, 1393–1403. [Google Scholar] [CrossRef] [PubMed]
- Cantanhede, I.G.; de Oliveira, J.R.M. PDGF Family Expression in Glioblastoma Multiforme: Data Compilation from Ivy Glioblastoma Atlas Project Database. Sci. Rep. 2017, 7, 15271. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Taylor, K.R.; Vinci, M.; Bullock, A.N.; Jones, C. ACVR1 mutations in DIPG: Lessons learned from FOP. Cancer Res. 2014, 74, 4565–4570. [Google Scholar] [CrossRef] [Green Version]
- Fortin, J.; Tian, R.; Zarrabi, I.; Hill, G.; Williams, E.; Sanchez-Duffhues, G.; Thorikay, M.; Ramachandran, P.; Siddaway, R.; Wong, J.F.; et al. Mutant ACVR1 Arrests Glial Cell Differentiation to Drive Tumorigenesis in Pediatric Gliomas. Cancer Cell 2020, 37, 308–323.e12. [Google Scholar] [CrossRef]
- Ascierto, P.A.; Kirkwood, J.M.; Grob, J.J.; Simeone, E.; Grimaldi, A.M.; Maio, M.; Palmieri, G.; Testori, A.; Marincola, F.M.; Mozzillo, N. The role of BRAF V600 mutation in melanoma. J. Transl. Med. 2012, 10, 85. [Google Scholar] [CrossRef] [Green Version]
- Ye, P.; Cai, P.; Xie, J.; Zhang, J. Reliability of BRAF mutation detection using plasma sample: A systematic review and meta-analysis. Medicine 2021, 100, e28382. [Google Scholar] [CrossRef]
- Natsumeda, M.; Chang, M.; Gabdulkhaev, R.; Takahashi, H.; Tsukamoto, Y.; Kanemaru, Y.; Okada, M.; Oishi, M.; Okamoto, K.; Rodriguez, F.J.; et al. Predicting BRAF V600E mutation in glioblastoma: Utility of radiographic features. Brain Tumor Pathol. 2021, 38, 228–233. [Google Scholar] [CrossRef]
- Castel, D.; Philippe, C.; Calmon, R.; Le Dret, L.; Truffaux, N.; Boddaert, N.; Pages, M.; Taylor, K.R.; Saulnier, P.; Lacroix, L.; et al. Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes. Acta Neuropathol. 2015, 130, 815–827. [Google Scholar] [CrossRef] [Green Version]
- Sloan, E.A.; Cooney, T.; Oberheim Bush, N.A.; Buerki, R.; Taylor, J.; Clarke, J.L.; Torkildson, J.; Kline, C.; Reddy, A.; Mueller, S.; et al. Recurrent non-canonical histone H3 mutations in spinal cord diffuse gliomas. Acta Neuropathol. 2019, 138, 877–881. [Google Scholar] [CrossRef] [Green Version]
- Haase, S.; Nunez, F.M.; Gauss, J.C.; Thompson, S.; Brumley, E.; Lowenstein, P.; Castro, M.G. Hemispherical Pediatric High-Grade Glioma: Molecular Basis and Therapeutic Opportunities. Int. J. Mol. Sci. 2020, 21, 9654. [Google Scholar] [CrossRef] [PubMed]
- Mizoguchi, M.; Yoshimoto, K.; Ma, X.; Guan, Y.; Hata, N.; Amano, T.; Nakamizo, A.; Suzuki, S.O.; Iwaki, T.; Sasaki, T. Molecular characteristics of glioblastoma with 1p/19q co-deletion. Brain Tumor Pathol. 2012, 29, 148–153. [Google Scholar] [CrossRef] [PubMed]
- Conway, J.R.; Warner, J.L.; Rubinstein, W.S.; Miller, R.S. Next-Generation Sequencing and the Clinical Oncology Workflow: Data Challenges, Proposed Solutions, and a Call to Action. JCO Precis. Oncol. 2019, 3. [Google Scholar] [CrossRef] [PubMed]
- Ozretic, L.; Heukamp, L.C.; Odenthal, M.; Buettner, R. The role of molecular diagnostics in cancer diagnosis and treatment. Onkologie 2012, 35, 8–12. [Google Scholar] [CrossRef]
- Pruneri, G.; De Braud, F.; Sapino, A.; Aglietta, M.; Vecchione, A.; Giusti, R.; Marchio, C.; Scarpino, S.; Baggi, A.; Bonetti, G.; et al. Next-Generation Sequencing in Clinical Practice: Is It a Cost-Saving Alternative to a Single-Gene Testing Approach? Pharm. Open 2021, 5, 285–298. [Google Scholar] [CrossRef]
Target | Chromosome | Number of Amplicons | Covered Bases | % Overall Coverage | Number of Exons |
---|---|---|---|---|---|
ACVR1 | chr2 | 23 | 1710 | 100 | 9 |
ATRX | chrX | 106 | 8161 | 99 | 35 |
BRAF | chr7 | 42 | 2655 | 99 | 18 |
CDKN2A | chr9 | 11 | 1008 | 99 | 5 |
EGFR | chr7 | 63 | 4489 | 100 | 30 |
H3F3A | chr1 | 5 | 273 | 58 | 3 |
HIST1H3B | chr6 | 5 | 431 | 100 | 1 |
HIST1H3C | chr6 | 5 | 431 | 100 | 1 |
IDH1 | chr2 | 20 | 1405 | 100 | 8 |
IDH2 | chr15 | 20 | 1572 | 99 | 11 |
TP53 | chr17 | 13 | 1503 | 100 | 12 |
PDGFRA | chr4 | 50 | 3710 | 100 | 22 |
PTEN | chr10 | 22 | 1901 | 98 | 10 |
TERT-Promoter | chr5 | 1 | 124 | 99 | n/a |
29 SNPs | chr1 | 30 | 30 | 100 | n/a |
25 SNPs | chr19 | 24 | 24 | 100 | n/a |
Sample ID | WHO Grade | Tumor Location | Sex | Age | MGMT | Idh1/21 | 1p/19q LOH 1 | TERT1 | Ki-67 (MIB-1) |
---|---|---|---|---|---|---|---|---|---|
ID 19 | IV | Right TI | M | 67 | 4% | wt | wt | - | 25% |
ID 48 | IV | Right F | M | 72 | 8% | wt | wt | - | 20% |
ID 78 | IV | Right T | F | 67 | 22% | wt | wt | - | 17% |
ID 93 | IV | Right F | M | 62 | 44% | wt | wt | - | 35% |
ID 41 | IV | Right TI | F | 45 | 23% | wt | wt | - | 37% |
ID 66 | IV | Right T | M | 47 | 63% | wt | wt | - | 30% |
ID 117 | IV | Right FTP | F | 56 | 67% | wt | wt | - | 30% |
ID 169 | IV | Right F | M | 52 | 13% | wt | wt | –146 C > T | 67% |
ID 121 | IV | Right P | M | 50 | 26% | wt | wt | - | 60% |
ID 143 | IV | Right F | M | 61 | 23% | wt | wt | –124 C > T | 30% |
ID 31 | IV | Left FP | M | 75 | 4% | wt | wt | - | 25% |
ID 30 | IV | Left PO | F | 76 | 41% | wt | wt | - | - |
ID 21 | IV | Right P | F | 54 | 49% | wt | wt | - | 80% |
ID 164 | IV | Right F | F | 63 | 2% | wt | wt | - | 40% |
ID 40 | IV | Right T | F | 76 | 27% | wt | wt | - | 35% |
ID 166 | IV | Left T | F | 73 | 4% | wt | wt | - | - |
ID 153 | III | Right F | F | 67 | 72% | p.R132H | LOH | - | 4% |
ID 209 | IV | Left P | M | 74 | 56% | p.R132H | LOH | - | 70% |
ID 232 | II | Left F | F | 48 | 53% | p.R132H | LOH | - | 5% |
ID 233 | IV | Right T | M | 42 | 60% | p.R132H | LOH | - | 20% |
ID 258 | II | Left T | M | 47 | 33% | p.R132H | LOH | - | 4% |
ID 260 | IV | Left CC | M | 41 | 5% | wt | LOH | - | - |
ID 278 | II | Left F | F | 52 | 35% | p.R132H | LOH | - | 1% |
ID 49 | IV | Left F | M | 51 | 32% | wt | wt | - | 50% |
ID 79 | IV | Right P | F | 71 | 28% | wt | wt | - | 20% |
ID 38 | IV | Right PO | M | 54 | 5% | wt | wt | - | 20% |
ID 192 | IV | Left T | F | 91 | - | wt | wt | - | - |
ID 199 | IV | Right F | M | 53 | - | wt | wt | - | - |
ID 176 | IV | Right F | M | 62 | 3% | wt | wt | - | - |
ID 104 | IV | Right F | F | 70 | 3% | wt | wt | - | 85% |
ID 09 | IV | Left FP | F | 81 | 4% | wt | 1p | - | 15% |
ID 10 | IV | Right FI | F | 63 | 9% | wt | 19q | - | 35% |
ID 85 | IV | Left P | M | 59 | 4% | wt | 19q | - | 30% |
ID sc21 | IV | Right P | M | 46 | 41% | wt | 1p | - | 60% |
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Guarnaccia, M.; Guarnaccia, L.; La Cognata, V.; Navone, S.E.; Campanella, R.; Ampollini, A.; Locatelli, M.; Miozzo, M.; Marfia, G.; Cavallaro, S. A Targeted Next-Generation Sequencing Panel to Genotype Gliomas. Life 2022, 12, 956. https://doi.org/10.3390/life12070956
Guarnaccia M, Guarnaccia L, La Cognata V, Navone SE, Campanella R, Ampollini A, Locatelli M, Miozzo M, Marfia G, Cavallaro S. A Targeted Next-Generation Sequencing Panel to Genotype Gliomas. Life. 2022; 12(7):956. https://doi.org/10.3390/life12070956
Chicago/Turabian StyleGuarnaccia, Maria, Laura Guarnaccia, Valentina La Cognata, Stefania Elena Navone, Rolando Campanella, Antonella Ampollini, Marco Locatelli, Monica Miozzo, Giovanni Marfia, and Sebastiano Cavallaro. 2022. "A Targeted Next-Generation Sequencing Panel to Genotype Gliomas" Life 12, no. 7: 956. https://doi.org/10.3390/life12070956