A High-Grade Glioma, Not Elsewhere Classified in an Older Adult with Discordant Genetic and Epigenetic Analyses
Abstract
1. Introduction
2. Detailed Case Description
3. Discussion
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
ATRX | alpha thalassemia/mental retardation syndrome X-linked |
BRAF | B-Raf proto-oncogene |
CDKN2A | cyclin-dependent kinase inhibitor 2A |
CNS | central nervous system |
EGFR | epidermal growth factor receptor |
FGFR1 | fibroblast growth factor receptor 1 |
GTR | gross total resection |
H3-3A | H3 histone family member 3 |
HGAP | high-grade astrocytoma with piloid features |
IDH | isocitrate dehydrogenase |
HGG | high-grade gliomas |
IHC | immunohistochemistry |
MAPK | mitogen-activated protein kinase |
MGMT | O6-methylguanine-DNA-methyltransferase |
NEC | not elsewhere classified |
NF1 | neurofibromatosis type 1 |
OS | overall survival |
PTEN | Phosphatase and TENsin homolog deleted on chromosome 10 |
RT | radiation therapy |
STR | subtotal resection |
TERT | telomerase reverse transcriptase |
WHO | World Health Organization |
References
- Capper, D.; Jones, D.T.W.; Sill, M.; Hovestadt, V.; Schrimpf, D.; Sturm, D.; Koelsche, C.; Sahm, F.; Chavez, L.; Reuss, D.E.; et al. DNA methylation-based classification of central nervous system tumours. Nature 2018, 555, 469–474. [Google Scholar] [CrossRef] [PubMed]
- Capper, D.; Stichel, D.; Sahm, F.; Jones, D.T.W.; Schrimpf, D.; Sill, M.; Schmid, S.; Hovestadt, V.; Reuss, D.E.; Koelsche, C.; et al. Practical implementation of DNA methylation and copy-number-based CNS tumor diagnostics: The Heidelberg experience. Acta Neuropathol. 2018, 136, 181–210. [Google Scholar] [CrossRef]
- Jaunmuktane, Z.; Capper, D.; Jones, D.T.W.; Schrimpf, D.; Sill, M.; Dutt, M.; Suraweera, N.; Pfister, S.M.; von Deimling, A.; Brandner, S. Methylation array profiling of adult brain tumours: Diagnostic outcomes in a large, single centre. Acta Neuropathol. Commun. 2019, 7, 24. [Google Scholar] [CrossRef]
- Tran, S.; Bielle, F. WHO 2021 and beyond: New types, molecular markers and tools for brain tumor classification. Curr. Opin. Oncol. 2022, 34, 670–675. [Google Scholar] [CrossRef] [PubMed]
- Moore, L.D.; Le, T.; Fan, G. DNA methylation and its basic function. Neuropsychopharmacology 2013, 38, 23–38. [Google Scholar] [CrossRef]
- 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-Oncology 2021, 23, 1231–1251. [Google Scholar] [CrossRef]
- Wenger, A.; Caren, H. Methylation Profiling in Diffuse Gliomas: Diagnostic Value and Considerations. Cancers 2022, 14, 5679. [Google Scholar] [CrossRef]
- Noushmehr, H.; Weisenberger, D.J.; Diefes, K.; Phillips, H.S.; Pujara, K.; Berman, B.P.; Pan, F.; Pelloski, C.E.; Sulman, E.P.; Bhat, K.P.; et al. Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell 2010, 17, 510–522. [Google Scholar] [CrossRef]
- Turcan, S.; Rohle, D.; Goenka, A.; Walsh, L.A.; Fang, F.; Yilmaz, E.; Campos, C.; Fabius, A.W.; Lu, C.; Ward, P.S.; et al. IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature 2012, 483, 479–483. [Google Scholar] [CrossRef] [PubMed]
- Fernandez, A.F.; Assenov, Y.; Martin-Subero, J.I.; Balint, B.; Siebert, R.; Taniguchi, H.; Yamamoto, H.; Hidalgo, M.; Tan, A.C.; Galm, O.; et al. A DNA methylation fingerprint of 1628 human samples. Genome Res. 2012, 22, 407–419. [Google Scholar] [CrossRef]
- Reinhardt, A.; Stichel, D.; Schrimpf, D.; Sahm, F.; Korshunov, A.; Reuss, D.E.; Koelsche, C.; Huang, K.; Wefers, A.K.; Hovestadt, V.; et al. Anaplastic astrocytoma with piloid features, a novel molecular class of IDH wildtype glioma with recurrent MAPK pathway, CDKN2A/B and ATRX alterations. Acta Neuropathol. 2018, 136, 273–291. [Google Scholar] [CrossRef] [PubMed]
- Pratt, D.; Abdullaev, Z.; Papanicolau-Sengos, A.; Ketchum, C.; Panneer Selvam, P.; Chung, H.J.; Lee, I.; Raffeld, M.; Gilbert, M.R.; Armstrong, T.S.; et al. High-grade glioma with pleomorphic and pseudopapillary features (HPAP): A proposed type of circumscribed glioma in adults harboring frequent TP53 mutations and recurrent monosomy 13. Acta Neuropathol. 2022, 143, 403–414. [Google Scholar] [CrossRef]
- Bender, K.; Perez, E.; Chirica, M.; Onken, J.; Kahn, J.; Brenner, W.; Ehret, F.; Euskirchen, P.; Koch, A.; Capper, D.; et al. High-grade astrocytoma with piloid features (HGAP): The Charite experience with a new central nervous system tumor entity. J. Neuro-Oncol. 2021, 153, 109–120. [Google Scholar] [CrossRef] [PubMed]
- Cimino, P.J.; Ketchum, C.; Turakulov, R.; Singh, O.; Abdullaev, Z.; Giannini, C.; Pytel, P.; Lopez, G.Y.; Colman, H.; Nasrallah, M.P.; et al. Expanded analysis of high-grade astrocytoma with piloid features identifies an epigenetically and clinically distinct subtype associated with neurofibromatosis type 1. Acta Neuropathol. 2023, 145, 71–82. [Google Scholar] [CrossRef] [PubMed]
- Rodriguez, F.J.; Brosnan-Cashman, J.A.; Allen, S.J.; Vizcaino, M.A.; Giannini, C.; Camelo-Piragua, S.; Webb, M.; Matsushita, M.; Wadhwani, N.; Tabbarah, A.; et al. Alternative lengthening of telomeres, ATRX loss and H3-K27M mutations in histologically defined pilocytic astrocytoma with anaplasia. Brain Pathol. 2019, 29, 126–140. [Google Scholar] [CrossRef] [PubMed]
- Soni, N.; Agarwal, A.; Ajmera, P.; Mehta, P.; Gupta, V.; Vibhute, M.; Gubbiotti, M.; Mark, I.T.; Messina, S.A.; Mohan, S.; et al. High-Grade Astrocytoma with Piloid Features: A Dual Institutional Review of Imaging Findings of a Novel Entity. AJNR Am. J. Neuroradiol. 2024, 45, 468–474. [Google Scholar] [CrossRef]
- Kline, C.N.; Joseph, N.M.; Grenert, J.P.; van Ziffle, J.; Talevich, E.; Onodera, C.; Aboian, M.; Cha, S.; Raleigh, D.R.; Braunstein, S.; et al. Targeted next-generation sequencing of pediatric neuro-oncology patients improves diagnosis, identifies pathogenic germline mutations, and directs targeted therapy. Neuro-Oncology 2017, 19, 699–709. [Google Scholar] [CrossRef]
- Zhang, Y.; Lucas, C.G.; Young, J.S.; Morshed, R.A.; McCoy, L.; Oberheim Bush, N.A.; Taylor, J.W.; Daras, M.; Butowski, N.A.; Villanueva-Meyer, J.E.; et al. Prospective genomically guided identification of “early/evolving” and “undersampled” IDH-wildtype glioblastoma leads to improved clinical outcomes. Neuro-Oncology 2022, 24, 1749–1762. [Google Scholar] [CrossRef]
- Jaiswal, S.; Fontanillas, P.; Flannick, J.; Manning, A.; Grauman, P.V.; Mar, B.G.; Lindsley, R.C.; Mermel, C.H.; Burtt, N.; Chavez, A.; et al. Age-related clonal hematopoiesis associated with adverse outcomes. N. Engl. J. Med. 2014, 371, 2488–2498. [Google Scholar] [CrossRef]
- Louis, D.N.; Wesseling, P.; Paulus, W.; Giannini, C.; Batchelor, T.T.; Cairncross, J.G.; Capper, D.; Figarella-Branger, D.; Lopes, M.B.; Wick, W.; et al. cIMPACT-NOW update 1: Not Otherwise Specified (NOS) and Not Elsewhere Classified (NEC). Acta Neuropathol. 2018, 135, 481–484. [Google Scholar] [CrossRef]
- Aldape, K.; Zadeh, G.; Mansouri, S.; Reifenberger, G.; von Deimling, A. Glioblastoma: Pathology, molecular mechanisms and markers. Acta Neuropathol. 2015, 129, 829–848. [Google Scholar] [CrossRef] [PubMed]
- 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] [PubMed]
- Brat, D.J.; Aldape, K.; Colman, H.; Holland, E.C.; Louis, D.N.; Jenkins, R.B.; Kleinschmidt-DeMasters, B.K.; Perry, A.; Reifenberger, G.; Stupp, R.; et al. cIMPACT-NOW update 3: Recommended diagnostic criteria for “Diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV”. Acta Neuropathol. 2018, 136, 805–810. [Google Scholar] [CrossRef] [PubMed]
- Tesileanu, C.M.S.; Dirven, L.; Wijnenga, M.M.J.; Koekkoek, J.A.F.; Vincent, A.; Dubbink, H.J.; Atmodimedjo, P.N.; Kros, J.M.; van Duinen, S.G.; Smits, M.; et al. Survival of diffuse astrocytic glioma, IDH1/2 wildtype, with molecular features of glioblastoma, WHO grade IV: A confirmation of the cIMPACT-NOW criteria. Neuro-Oncology 2020, 22, 515–523. [Google Scholar] [CrossRef]
- WHO Classification of Tumours Editorial Board. Central Nervous System Tumours; International Agency for Research on Cancer, World Health Organization: Lyon, France, 2021. [Google Scholar]
- Cancer Genome Atlas Research, N.; Brat, D.J.; Verhaak, R.G.; Aldape, K.D.; Yung, W.K.; Salama, S.R.; Cooper, L.A.; Rheinbay, E.; Miller, C.R.; Vitucci, M.; et al. Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas. N. Engl. J. Med. 2015, 372, 2481–2498. [Google Scholar] [CrossRef]
- Raghu, A.L.B.; Chen, J.A.; Valdes, P.A.; Essayed, W.; Claus, E.; Arnaout, O.; Smith, T.R.; Chiocca, E.A.; Peruzzi, P.P.; Bernstock, J.D. Cerebellar High-Grade Glioma: A Translationally Oriented Review of the Literature. Cancers 2022, 15, 174. [Google Scholar] [CrossRef]
- Zander, C.; Diebold, M.; Shah, M.J.; Malzkorn, B.; Prinz, M.; Urbach, H.; Erny, D.; Taschner, C.A. Freiburg Neuropathology Case Conference: 68-Year-Old Patient with Slurred Speech, Double Vision, and Increasing Gait Disturbance. Clin. Neuroradiol. 2024, 34, 279–286. [Google Scholar] [CrossRef]
- Nawa, S.; Ohka, F.; Motomura, K.; Takeuchi, K.; Nagata, Y.; Yamaguchi, J.; Saito, R. Obstructive Hydrocephalus Due to Aggressive Posterior Fossa Tumor Exhibiting Histological Characteristics of Pilocytic Astrocytoma in Two Adult Neurofibromatosis Type 1 (NF1) Cases. Cureus 2024, 16, e58697. [Google Scholar] [CrossRef]
- Gareton, A.; Tauziede-Espariat, A.; Dangouloff-Ros, V.; Roux, A.; Saffroy, R.; Castel, D.; Kergrohen, T.; Fina, F.; Figarella-Branger, D.; Pages, M.; et al. The histomolecular criteria established for adult anaplastic pilocytic astrocytoma are not applicable to the pediatric population. Acta Neuropathol. 2020, 139, 287–303. [Google Scholar] [CrossRef]
- Lassman, A.B.; Sepulveda-Sanchez, J.M.; Cloughesy, T.F.; Gil-Gil, M.J.; Puduvalli, V.K.; Raizer, J.J.; De Vos, F.Y.F.; Wen, P.Y.; Butowski, N.A.; Clement, P.M.J.; et al. Infigratinib in Patients with Recurrent Gliomas and FGFR Alterations: A Multicenter Phase II Study. Clin. Cancer Res. 2022, 28, 2270–2277. [Google Scholar] [CrossRef]
- Loilome, W.; Joshi, A.D.; ap Rhys, C.M.; Piccirillo, S.; Vescovi, A.L.; Gallia, G.L.; Riggins, G.J. Glioblastoma cell growth is suppressed by disruption of Fibroblast Growth Factor pathway signaling. J. Neuro-Oncol. 2009, 94, 359–366. [Google Scholar] [CrossRef]
- Yoza, K.; Himeno, R.; Amano, S.; Kobashigawa, Y.; Amemiya, S.; Fukuda, N.; Kumeta, H.; Morioka, H.; Inagaki, F. Biophysical characterization of drug-resistant mutants of fibroblast growth factor receptor 1. Genes Cells 2016, 21, 1049–1058. [Google Scholar] [CrossRef]
- Stupp, R.; Mason, W.P.; van den Bent, M.J.; Weller, M.; Fisher, B.; Taphoorn, M.J.; Belanger, K.; Brandes, A.A.; Marosi, C.; Bogdahn, U.; et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med. 2005, 352, 987–996. [Google Scholar] [CrossRef] [PubMed]
- Whitfield, B.T.; Huse, J.T. Classification of adult-type diffuse gliomas: Impact of the World Health Organization 2021 update. Brain Pathol. 2022, 32, e13062. [Google Scholar] [CrossRef]
- Cimmino, F.; Montella, A.; Tirelli, M.; Avitabile, M.; Lasorsa, V.A.; Visconte, F.; Cantalupo, S.; Maiorino, T.; De Angelis, B.; Morini, M.; et al. FGFR1 is a potential therapeutic target in neuroblastoma. Cancer Cell Int. 2022, 22, 174. [Google Scholar] [CrossRef] [PubMed]
- Sabbagh, M.F.; Janovitz, T.; Dias-Santagata, D.; Siegmund, S.E.; Nardi, V.; Wirth, L.J.; Randolph, G.W.; Lennerz, J.K.; Decker, B.; Nose, V.; et al. FGFR Alterations in Thyroid Carcinoma: A Novel Class of Primary Drivers with Significant Therapeutic Implications and Secondary Molecular Events Potentially Mediating Resistance in Thyroid Malignancy. Thyroid 2024. [Google Scholar] [CrossRef] [PubMed]
Author/Year | Age/Sex | Location | Molecular Alterations | Surgery (s) | RT (Gy) | PFS (m) | OS (m) |
---|---|---|---|---|---|---|---|
Yuen et al., 2024 | 72/M | Temporal lobe | CDKN2A/B homozygous deletion FGFR1 p.N546K ATRX loss (on IHC) BRAF, NF1, KRAS, IDH1, IDH2, H3-3A, TERT, EGFR, PTEN, PDGFRA–wild-type | NTR | 60 | 15 | alive at 15 m follow-up |
Bender et al., 2021 [13] | 71/M | Spinal cord | CDKN2A/B deletion ATRX loss (on IHC) FGFR1 complex rearrangement IDH 1/2 wild-type MGMT unmethylated | STR → GTR | 50.4 | 3.6 | alive at 14.6 m follow-up |
49/F | Pons Cerebellar peduncle | CDKN2A/B deletion ATRX loss (on IHC) IDH1 R132H IHC negative MGMT unmethylated | biopsy | 54 | 7.6 | 9.1 | |
67/M | Spinal cord | CDKN2A/B deletion ATRX loss (on IHC) IDH 1/2 wild-type MGMT unmethylated | STR | n/a | n/a | n/a | |
53/M | Brainstem | CDKN2A/B deletion ATRX retained (on IHC) IDH 1/2 wild-type H3-3A wild-type BRAF V600 hotspot-wild-type MGMT methylated | STR | 54 | n/a | 18.6 | |
47/M | Mesencephalon—diencephalon | NF1 syndrome CDKN2A/B deletion ATRX loss (on IHC) MGMT unmethylated | bx | n/a | n/a | 1.8 | |
44/M | Parieto- occipital | NF1 mutation in the setting of NF1 syndrome CDKN2A/B deletion ATRX retained (on IHC) IDH1 R132H IHC negative H3 K27M IHC negative BRAF V600 wild-type, MGMT methylated | STR → STR | 59.2 | 5.4 | 14.8 | |
Cimino et al., 2023 [14] (n = 144) | 43 (mean)/ F (n = 59), M (n = 85) | Posterior fossa (81/130, 62%) Supratentorial (34/130, 26%) Spinal Cord (13/130, 10%) | CDKN2A deletion (84.1%) ATRX mutation or loss on IHC (58.6%) NF1 alterations (40.4%) FGFR1 alterations (33.1%) BRAF alterations (20.9%) KRAS (1.1%) | n/a | n/a | n/a | n/a |
Reinhardt et al., 2018 [11] (n = 102) | 41.5 (median)/ F (n = 40), M (n = 43) | Posterior fossa (74%) | CDKN2A/B deletion (66/83, 80%) ATRX mutations/loss on IHC (33/74, 45%) NF1 alterations (20/67, 30%) BRAF fusion (15/74, 20%) FGFR1 alterations (12/64, 19%) KRAS mutation (2/64, 3%) IDH 1/2 wild-type (100%) MGMT methylated (38/83, 46%) | n/a | n/a | n/a | n/a |
Nawa et al., 2024 [29] | 34/M | Cerebellum/pons | CDKN2A/B homozygous deletion | STR | 54 | 16 | n/a |
37/F | Cerebellum, spinal cord | CDKN2A/B homozygous deletion | STR | 60 | 12 | n/a | |
Gareton et al., 2020 [30] | 8/F | Supratentorial Parietal lobe | ATRX retained (on IHC) CDKN2A intact FGFR1 p.K678E RAD50 p.R365Q MDM2 amplification Monosomy 10q | GTR | RT dose n/a | 13.4 | 37 |
Zander et al., 2024 [28] | 68/M | Cerebellum | NF1 truncating mutation CDKN2A deletion (likely not homozygous) ATRX retained (on IHC) BRAF, IDH1, IDH2, H3-3A, TERT wild-type | GTR | n/a | n/a | n/a |
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Yuen, C.A.; Bao, S.; Kong, X.-T.; Terry, M.; Himstead, A.; Zheng, M.; Pekmezci, M. A High-Grade Glioma, Not Elsewhere Classified in an Older Adult with Discordant Genetic and Epigenetic Analyses. Biomedicines 2024, 12, 2042. https://doi.org/10.3390/biomedicines12092042
Yuen CA, Bao S, Kong X-T, Terry M, Himstead A, Zheng M, Pekmezci M. A High-Grade Glioma, Not Elsewhere Classified in an Older Adult with Discordant Genetic and Epigenetic Analyses. Biomedicines. 2024; 12(9):2042. https://doi.org/10.3390/biomedicines12092042
Chicago/Turabian StyleYuen, Carlen A., Silin Bao, Xiao-Tang Kong, Merryl Terry, Alexander Himstead, Michelle Zheng, and Melike Pekmezci. 2024. "A High-Grade Glioma, Not Elsewhere Classified in an Older Adult with Discordant Genetic and Epigenetic Analyses" Biomedicines 12, no. 9: 2042. https://doi.org/10.3390/biomedicines12092042
APA StyleYuen, C. A., Bao, S., Kong, X.-T., Terry, M., Himstead, A., Zheng, M., & Pekmezci, M. (2024). A High-Grade Glioma, Not Elsewhere Classified in an Older Adult with Discordant Genetic and Epigenetic Analyses. Biomedicines, 12(9), 2042. https://doi.org/10.3390/biomedicines12092042