Evaluation of DNA Methylation Array for Glioma Tumor Profiling and Description of a Novel Epi-Signature to Distinguish IDH1/IDH2 Mutant and Wild-Type Tumors
Abstract
:1. Introduction
2. Methods
2.1. Sample Selection
2.2. Immunohistochemistry for IDH1 R132H
2.3. 1p19q LOH Testing
2.4. Whole-Genome Methylation Array and CIMP Analysis
2.5. Copy Number Analysis
2.6. Brain Tumor Methylation Classifier
2.7. Next-Generation Sequencing
3. Results
3.1. Cohort Demographics
3.2. WGMA and CIMP
3.3. 1p19q Co-Deletion Analysis
3.4. Brain Tumor Methylation Classifier
3.5. Refinement of Glioma Classification Using Genomic Information
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
- Ostrom, Q.T.; Cioffi, G.; Gittleman, H.; Patil, N.; Waite, K.; Kruchko, C.; Barnholtz-Sloan, J.S. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2012–2016. Neuro Oncol. 2019, 21 (Suppl. 5), v1–v100. [Google Scholar] [CrossRef]
- Louis, D.N.; Perry, A.; Reifenberger, G.; Von Deimling, A.; Figarella-Branger, D.; Cavenee, W.K.; Ohgaki, H.; Wiestler, O.D.; Kleihues, P.; Ellison, D.W. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: A summary. Acta Neuropathol. 2016, 131, 803–820. [Google Scholar] [CrossRef] [Green Version]
- Louis, D.N.; Ohgaki, H.; Wiestler, O.D.; Cavenee, W.K.; Burger, P.C.; Jouvet, A.; Scheithauer, B.W.; Kleihues, P. The 2007 WHO Classification of Tumours of the Central Nervous System. Acta Neuropathol. 2007, 114, 97–109. [Google Scholar] [CrossRef] [Green Version]
- 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]
- Suzuki, H.; Aoki, K.; Chiba, K.; Sato, Y.; Shiozawa, Y.; Shiraishi, Y.; Shimamura, T.; Niida, A.; Motomura, K.; Ohka, F.; et al. Mutational landscape and clonal architecture in grade II and III gliomas. Nat. Genet. 2015, 47, 458–468. [Google Scholar] [CrossRef]
- Weller, M.; Weber, R.; Willscher, E.; Riehmer, V.; Hentschel, B.; Kreuz, M.; Felsberg, J.; Beyer, U.; Löffler-Wirth, H.; Kaulich, K.; et al. Molecular classification of diffuse cerebral WHO grade II/III gliomas using genome- and transcriptome-wide profiling improves stratification of prognostically distinct patient groups. Acta Neuropathol. 2015, 129, 679–693. [Google Scholar] [CrossRef] [Green Version]
- Yan, H.; Parsons, D.W.; Jin, G.; McLendon, R.; Rasheed, B.A.; Yuan, W.; Kos, I.; Batinic-Haberle, I.; Jones, S.; Riggins, G.J.; et al. IDH1 and IDH2 Mutations in Gliomas. N. Engl. J. Med. 2009, 360, 765–773. [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] [PubMed] [Green Version]
- Turcan, S.; Rohle, D.; Goenka, A.; Walsh, L.; Fang, F.; Yilmaz, E.; Campos, C.; Fabius, A.W.M.; Lu, C.; Ward, P.; et al. IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature 2012, 483, 479–483. [Google Scholar] [CrossRef] [Green Version]
- 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]
- Marzouka, N.-A.; Nordlund, J.; Bäcklin, C.L.; Lönnerholm, G.; Syvänen, A.-C.; Almlöf, J.C. CopyNumber450kCancer: Baseline correction for accurate copy number calling from the 450k methylation array. Bioinformatics 2016, 32, 1080–1082. [Google Scholar] [CrossRef] [Green Version]
- 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] [Green Version]
- Karimi, S.; Zuccato, J.A.; Mamatjan, Y.; Mansouri, S.; Suppiah, S.; Nassiri, F.; Diamandis, P.; Munoz, D.G.; Aldape, K.D.; Zadeh, G. The central nervous system tumor methylation classifier changes neuro-oncology practice for challenging brain tumor diagnoses and directly impacts patient care. Clin. Epigenet. 2019, 11, 185. [Google Scholar] [CrossRef] [Green Version]
- Louis, D.N.; Wesseling, P.; Brandner, S.; Brat, D.J.; Ellison, D.W.; Giangaspero, F.; Hattab, E.M.; Hawkins, C.; Judge, M.J.; Kleinschmidt-DeMasters, B.; et al. Data Sets for the Reporting of Tumors of the Central Nervous System: Recommendations From The International Collaboration on Cancer Reporting. Arch. Pathol. Lab. Med. 2020, 144, 196–206. [Google Scholar] [CrossRef] [Green Version]
- Riemenschneider, M.J.; Hegi, M.E.; Reifenberger, G. MGMT promoter methylation in malignant gliomas. Target. Oncol. 2010, 5, 161–165. [Google Scholar] [CrossRef]
- Reifenberger, J.; Reifenberger, G.; Liu, L.; James, C.D.; Wechsler, W.; Collins, V.P. Molecular genetic analysis of oligoden-droglial tumors shows preferential allelic deletions on 19q and 1p. Am. J. Pathol. 1994, 145, 1175–1190. [Google Scholar] [PubMed]
- Wiestler, B.; Capper, D.; Holland-Letz, T.; Korshunov, A.; Von Deimling, A.; Pfister, S.M.; Platten, M.; Weller, M.; Wick, W. ATRX loss refines the classification of anaplastic gliomas and identifies a subgroup of IDH mutant astrocytic tumors with better prognosis. Acta Neuropathol. 2013, 126, 443–451. [Google Scholar] [CrossRef] [Green Version]
- Paul, Y.; Mondal, B.; Patil, V.; Somasundaram, K. DNA methylation signatures for 2016 WHO classification subtypes of diffuse gliomas. Clin. Epigenetics 2017, 9, 32. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Christensen, B.C.; Smith, A.A.; Zheng, S.; Koestler, D.C.; Houseman, E.A.; Marsit, C.; Wiemels, J.L.; Nelson, H.; Karagas, M.R.; Wrensch, M.R.; et al. DNA Methylation, Isocitrate Dehydrogenase Mutation, and Survival in Glioma. JNCI J. Natl. Cancer Inst. 2011, 103, 143–153. [Google Scholar] [CrossRef]
- Ichimura, N.; Shinjo, K.; An, B.; Shimizu, Y.; Yamao, K.; Ohka, F.; Katsushima, K.; Hatanaka, A.; Tojo, M.; Yamamoto, E.; et al. Aberrant TET1 Methylation Closely Associated with CpG Island Methylator Phenotype in Colorectal Cancer. Cancer Prev. Res. 2015, 8, 702–711. [Google Scholar] [CrossRef]
- Yagi, K.; Akagi, K.; Hayashi, H.; Nagae, G.; Tsuji, S.; Isagawa, T.; Midorikawa, Y.; Nishimura, Y.; Sakamoto, H.; Seto, Y.; et al. Three DNA Methylation Epigenotypes in Human Colorectal Cancer. Clin. Cancer Res. 2010, 16, 21–33. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Weisenberger, D.J. Characterizing DNA methylation alterations from The Cancer Genome Atlas. J. Clin. Investig. 2014, 124, 17–23. [Google Scholar] [CrossRef] [Green Version]
- Li, K.K.-W.; Shi, Z.-F.; Malta, T.M.; Chan, A.K.-Y.; Cheng, S.; Kwan, J.S.H.; Yang, R.R.; Poon, W.S.; Mao, Y.; Noushmehr, H.; et al. Identification of subsets of IDH-mutant glioblastomas with distinct epigenetic and copy number alterations and stratified clinical risks. Neuro Oncol. Adv. 2019, 1, vdz015. [Google Scholar] [CrossRef] [Green Version]
- Vega, S.F.; Wenger, A.; Kling, T.; Bontell, T.O.; Jakola, A.S.; Carén, H. Spatial heterogeneity in DNA methylation and chromosomal alterations in diffuse gliomas and meningiomas. Mod. Pathol. 2022, 35, 1551–1561. [Google Scholar] [CrossRef]
- Yang, J.; Wang, Q.; Zhang, Z.-Y.; Long, L.; Ezhilarasan, R.; Karp, J.M.; Tsirigos, A.; Snuderl, M.; Wiestler, B.; Wick, W.; et al. DNA methylation-based epigenetic signatures predict somatic genomic alterations in gliomas. Nat. Commun. 2022, 13, 4410. [Google Scholar] [CrossRef]
- Liu, Q.; Reed, M.; Zhu, H.; Cheng, Y.; Almeida, J.; Fruhbeck, G.; Ribeiro, R.; Hu, P. Epigenome-wide DNA methylation and transcriptome profiling of localized and locally advanced prostate cancer: Uncovering new molecular markers. Genomics 2022, 2022, 110474. [Google Scholar] [CrossRef]
- Gao, Y.; Zhao, H.; An, K.; Liu, Z.; Hai, L.; Li, R.; Zhou, Y.; Zhao, W.; Jia, Y.; Wu, N.; et al. Whole-genome bisulfite sequencing analysis of circulating tumour DNA for the detection and molecular classification of cancer. Clin. Transl. Med. 2022, 12, e1014. [Google Scholar] [CrossRef]
- Gu, X.; Huang, X.; Zhang, X.; Wang, C. Development and Validation of a DNA Methylation-related Classifier of Circulating Tumour Cells to Predict Prognosis and to provide a therapeutic strategy in Lung Adenocarcinoma. Int. J. Biol. Sci. 2022, 18, 4984–5000. [Google Scholar] [CrossRef]
Probeset ID | Gene Symbol | Location within Gene | Genomic Location (hg19) | p-Value | Methylation Estimate Value | F Value |
---|---|---|---|---|---|---|
cg25042239 | CUL7 | 5′UTR | Chr 6: 43021668 | 4.03E-06 | 15.2 | 27.6 |
cg12624667 | TRANK1 | TSS200 | Chr 3: 36986555 | 9.81E-06 | 17 | 26.8 |
cg07003542 | SNCB | 5′UTR | Chr 5: 176056682 | 8.97E-06 | 16.7 | 26.1 |
cg13147822 | MECOM | TSS1500 | Chr 3: 168864313 | 2.19E-05 | 17.3 | 25.9 |
cg11952858 | SLX1A | Body | Chr 16: 30206082 | 2.56E-05 | 15.5 | 25.6 |
cg13655082 | intergenic | Not applicable | Chr 9: 125109046 | 1.37E-05 | 15.4 | 23.4 |
cg02870222 | TICAM2 | TSS200 | Chr 5: 114938179 | 1.58E-04 | 17.3 | 22.7 |
cg13212283 | NDUFA4L2 | 5′UTR | Chr 12: 57632120 | 1.19E-04 | 17.8 | 22.5 |
cg26325335 | CACNA2D2 | Body | Chr 3: 50402333 | 2.30E-04 | 16.2 | 22.4 |
cg03027661 | ZNRF3 | Body | Chr 22: 29426832 | 4.06E-05 | 15.7 | 21.1 |
cg15986590 | KLF16 | Body | Chr 19: 1862404 | 2.20E-04 | 15.5 | 20.5 |
Sample # | IHC Result (p.R132H) | NGS (IDH1/IDH2) | CIMP (Meth Array) | 1p LOH | 1p del (Meth Array) | 19q LOH | 19q del (Meth Array) | Other Apparent CNV (Meth Array) | Molcucular Pathology Classifier | Original Histopathology Classification | Reclassification as Per WHO 2021 |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | -- | -- | -- | plexus tumor, subclass pediatric B (0.5; 0.47) | Oligodendroglioma, grade II | Oligodendroglioma, IDH mutant, 1p19q co-deleted | |||||
2 | -- | -- | -- | plexus tumor, subclass pediatric B (0.48; 0.46) | Oligodendroglioma, grade II | Astrocytoma, IDH mutant | |||||
3 | −7, −13, −18, +10 | IDH glioma, subclass 1p/19q codeleted oligodendrioma (0.56; 0.47) | Oligodendroglioma, grade II | Oligodendroglioma, IDH mutant, 1p19q co-deleted | |||||||
4 | −7, −13, −18, +10, +22 | plexus tumor, subclass pediatric B (0.31; 0.25) | Oligodendroglioma, grade II | Astrocytoma, IDH mutant | |||||||
5 | −7p partial, −7q, −9p, −11q partial, +14, +19, +22 partial | glioblastoma, IDH wildtype, subclass RTK I (0.99; 0.75) | Oligodendroglioma, grade III | Glioblastoma, IDH wild-type | |||||||
6 | −7, −13 partial, +14 partial, −18, −22 | glioblastoma, IDH wildtype, subclass RTK I (0.48; 0.36) | Oligodendroglioma, grade III | Glioblastoma, IDH wild-type | |||||||
7 | +6q, −10, +13, −14 partial, +14 partial, +18, +20, −22, | glioblastoma, IDH wildtype, subclass RTK (0.99; 0.52) | Oligodendroglioma, grade III | Glioblastoma, IDH wild-type | |||||||
8 | +10, +13, +14 partial, −18, −20 | glioblastoma, IDH wildtype, subclass mesenchymal (0,43; 0.36) | Oligodendroglioma, grade III | Glioblastoma, IDH wild-type | |||||||
9 | ** | -- | -- | -- | methylation class glioblastoma, IDH wildtype, subclass RTK I (0.51; 0.49) | Oligodendroglioma, grade III | Glioblastoma, IDH wild-type | ||||
10 | +7, +9, +14, −18, −20, +22 | methylation class glioblastoma, IDH wildtype, subclass RTK I (0.35; 0.2) | Oligodendroglioma, grade III | Glioblastoma, IDH wild-type | |||||||
11 | −1q, +2p,−2q, −3q partial, +4p, −7p, +8, +9p, +10p, −13, −18, +21, −21 partial, +22 | methylation class glioblastoma, IDH wildtype, H3.3 G34 mutant (0.99; NA) | Oligodendroglioma, grade III | Glioblastoma, IDH wild-type | |||||||
12 | +7, −8p partial, −9p, +10, −13, +14, +20 | No matching methylation classes with calibrated with score ≥ 0.3 | Oligodendroglioma, grade III | Glioblastoma, IDH wild-type | |||||||
13 | -- | -- | -- | methylation class plexus tumor, subclass pediatric B (0.56; 0.54) | Glioblastoma | Glioblastoma, IDH wild-type | |||||
14 | query EGFR amp, −10p, +10q partial, −10q partial, +11p partial, +14, +19q, +22 | methylation class glioblastoma, IDH wildtype, subclass RTK II (0.73; 0.47) | Glioblastoma | Glioblastoma, IDH wild-type | |||||||
15 | +7q, +19, +21 | methylation class plexus tumor, subclass pediatric B (0.44; 0.4) | Glioblastoma | Glioblastoma, IDH wild-type | |||||||
16 | −1p partial, −6q partial, +7p, −7q, +9p partial, −13q partial, −14q partial, −15q partial, +16p, −16q, +22 | No matching methylation classes with calibrated with score ≥ 0.3 | Glioblastoma | Glioblastoma, IDH wild-type | |||||||
17 | +3, −4pter, +6p, −6q, query EGFR amp, +9q, +13, +14, −16, +19q, +22 | methylation class glioblastoma, IDH wildtype, subclass RTK II (0.41; 0.17) | Glioblastoma | Glioblastoma, IDH wild-type | |||||||
18 | +6q, −7p, +10q, +13, +16q, +17, +19, +20 | methylation class glioblastoma, IDH wildtype, subclass RTK II (0.82; 0.53) | Glioblastoma | Glioblastoma, IDH wild-type | |||||||
19 | -- | -- | -- | methylation class plexus tumor, subclass pediatric B (0.51; 0.49) | Glioblastoma | Glioblastoma, IDH wild-type | |||||
20 | -- | -- | -- | methylation class plexus tumor, subclass pediatric B (0.52; 0.52) | Glioblastoma | Glioblastoma, IDH wild-type | |||||
21 | *** | -- | -- | -- | methylation class family Plexus Tumor (0.42; 0.4) | Oligoastrocytoma, grade II | Astrocytoma, IDH mutant | ||||
22 | -- | -- | -- | -- | methylation class plexus tumor, subclass pediatric B (0.45; 0.43) | Oligoastrocytoma, grade II | Astrocytoma, IDH mutant | ||||
23 | -- | -- | -- | methylation class IDH glioma, subclass 1p/19q codeleted oligodendroglioma (0.93; 0.9) | Oligoastrocytoma, grade II | Oligodendroglioma, IDH mutant, 1p19q co-deleted | |||||
24 | -- | -- | -- | -- | methylation class plexus tumor, subclass pediatric B (0.5; 0.48) | Oligoastrocytoma, grade II | Oligodendroglioma, IDH mutant, 1p19q co-deleted | ||||
25 | methylation class plexus tumor, subclass pediatric B (0.42; 0.4) | Oligoastrocytoma, grade II | Astrocytoma, IDH mutant | ||||||||
26 | -- | -- | -- | methylation class plexus tumor, subclass pediatric B (0.47; 0.45) | Oligoastrocytoma, grade III | Anaplastic astrocytoma, IDH-wildtype (WHO grade 3) | |||||
27 | -- | -- | -- | methylation class plexus tumor, subclass pediatric B (0.35; 0.32) | Oligoastrocytoma, grade III | Astrocytoma, IDH mutant | |||||
28 | −7p, −9p, +10, −15, −18, +19p, | IDH glioma, subclass 1p/19q codeleted (0.9; 0.81) | Oligoastrocytoma, grade III | Oligodendroglioma, IDH mutant, 1p19q co-deleted | |||||||
29 | −4, −7, −9p, query +10, −12p, −12q partial, +22 | methylation class IDH glioma, subclass 1p/19q codeleted oligodendroglioma (0.99; 0.98) | Oligoastrocytoma, grade III | Oligodendroglioma, IDH mutant, 1p19q co-deleted | |||||||
30 | **** | * | −4, −18, query −9 | No matching methylation clase s with calibrated score >= 0.3 | Oligodendroglioma, grade II | Oligodendroglioma, IDH mutant, 1p19q co-deleted | |||||
31 | -- | -- | -- | No matching methylation clase s with calibrated score >= 0.3 | Oligodendroglioma, grade II | Diffuse astrocytoma, IDH-wildtype (WHO grade 2) | |||||
32 | −1q partial, −5p partial, −7, −9p partial, −13, +14, −18, +19, +22 | methylation class glioblastoma, IDH wildtype, subclass RTK II (0.41; 0.2) | Oligodendroglioma, grade III | Anaplastic astrocytoma, IDH-wildtype (WHO grade 3) | |||||||
33 | -- | -- | -- | -- | methylation class plexus tumor, subclass pediatric B (0.39; 0.2) | Glioblastoma | Glioblastoma, NES | ||||
34 | -- | -- | -- | methylation class plexus tumor, subclass pediatric B (0.43; 0.41) | Oligoastrocytoma, grade II | Oligodendroglioma, IDH mutant, 1p19q co-deleted | |||||
35 | +3, +9p partial, +9q, +12, +17 | Plexus tumor, subclass pediatric B (0.49; 0.46) | Glioblastoma | Glioblastoma, IDH wild-type | |||||||
36 | -- | -- | -- | -- | methylation class plexus tumor, subclass pediatric B (0.42; 0.4) | Oligoastrocytoma, grade II | Diffuse astrocytoma, IDH-wildtype (WHO grade 2) | ||||
37 | -- | -- | -- | No matching methylation clase s with calibrated score >= 0.3 | Oligoastrocytoma, grade III | Anaplastic astrocytoma, IDH-wildtype (WHO grade 3) | |||||
38 | −1q partial, +1q partial, +6p, −6q, +10p, −13, query low level +16p, −16q, query low level 19q gain, +21, +22 | Gliobastoma, IDH wildtype, subclass mesenchymal (0.98; 0.64) | Oligoastrocytoma, grade III | Anaplastic astrocytoma, IDH-wildtype (WHO grade 3) | |||||||
39 | −1p partial, +1p partial, +1q, −5q partial, −7q partial, −14q partial, +14q partial, −15q partial, +15q partial, −16p, +16q, +22 | No matching methylation clase s with calibrated score >= 0.3 | Oligoastrocytoma, grade III | Anaplastic astrocytoma, IDH-wildtype (WHO grade 3) | |||||||
40 | -- | -- | +2, +3q partial, +4q partial, +6q, +8, +10q partial, +14, +22 | Glioblastoma, IDH methylation wildtype, subclass RTK II (0.99; 0.57) | Glioblastoma | Glioblastoma, IDH wild-type | |||||
41 | -- | -- | −1p partial, −1q partial, +4q partial, +6q partial, −9p partial, −9q partial, 10q gain partial, +13, +14, +18q, +19p, +20, −21, +22 | Glioblastoma, IDH wildtype, subclass mesenchymal (0.98; 0.94) | -- | Glioblastoma, IDH wild-type | |||||
42 | −2, +3q partial, −6p, +7p, EGFR amp, −7q, −8p, −9p partial−10, +10q partial, −11, +14, −15, −16, +18, +19, +20, +22 | methylation class glioblastoma, IDH wildtype, subclass RTK I (0.99; 0.82) | Oligodendroglioma, grade III | Glioblastoma, IDH wild-type | |||||||
43 | −1p partial, −1q partial, −3p partial, −3q partial, −4q partial, −6q, −9p partial, −10 partial, −13 partial, −14, −18q, −22 | methylation class glioblastoma, IDH wildtype, subclass RTK II (0.99; 0.81) | Glioblastoma | Glioblastoma, IDH wild-type | |||||||
44 | -- | −7, +10, +14, +22 | methylation class IDH glioma, subclass 1p/19q codeleted oligodendroglioma (0.99; 0.99) | Oligodendroglioma, grade II | Oligodendroglioma, IDH mutant, 1p19q co-deleted | ||||||
45 | -- | −2, −3, −5, −7, +10, −11p, −12, −13, −15, −17, +18, +22 | methylation class IDH glioma, subclass high grade astrocytoma (0.99; 0.91) | Oligodendroglioma, grade III | Astrocytoma, IDH mutant, grade 4 | ||||||
46 | -- | +3p partial, +3q partial, +4q partial, +6q, +9p partial, +10, −10q partial, +13q partial, +14, +18q, +22 | methylation class glioblastoma, IDH wildtype, subclass RTK I (0.99; 0.95) | Glioblastoma | Glioblastoma, IDH wild-type | ||||||
47 | -- | +6q, −7, +10, +13 | methylation class control tissue, hemispheric cortex (0.95, NA) | Oligodendroglioma, grade II | Diffuse astrocytoma, IDH-wildtype (WHO grade 2) | ||||||
48 | -- | −9p, −10q | methylation class glioblastoma, IDH wildtype, subclass RTK II (0.99; 0.83) | Oligodendroglioma, grade III | Glioblastoma, IDH wild-type |
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Schenkel, L.C.; Mathew, J.; Hirte, H.; Provias, J.; Paré, G.; Chong, M.; Grafodatskaya, D.; McCready, E. Evaluation of DNA Methylation Array for Glioma Tumor Profiling and Description of a Novel Epi-Signature to Distinguish IDH1/IDH2 Mutant and Wild-Type Tumors. Genes 2022, 13, 2075. https://doi.org/10.3390/genes13112075
Schenkel LC, Mathew J, Hirte H, Provias J, Paré G, Chong M, Grafodatskaya D, McCready E. Evaluation of DNA Methylation Array for Glioma Tumor Profiling and Description of a Novel Epi-Signature to Distinguish IDH1/IDH2 Mutant and Wild-Type Tumors. Genes. 2022; 13(11):2075. https://doi.org/10.3390/genes13112075
Chicago/Turabian StyleSchenkel, Laila C., Joseph Mathew, Hal Hirte, John Provias, Guillaume Paré, Michael Chong, Daria Grafodatskaya, and Elizabeth McCready. 2022. "Evaluation of DNA Methylation Array for Glioma Tumor Profiling and Description of a Novel Epi-Signature to Distinguish IDH1/IDH2 Mutant and Wild-Type Tumors" Genes 13, no. 11: 2075. https://doi.org/10.3390/genes13112075
APA StyleSchenkel, L. C., Mathew, J., Hirte, H., Provias, J., Paré, G., Chong, M., Grafodatskaya, D., & McCready, E. (2022). Evaluation of DNA Methylation Array for Glioma Tumor Profiling and Description of a Novel Epi-Signature to Distinguish IDH1/IDH2 Mutant and Wild-Type Tumors. Genes, 13(11), 2075. https://doi.org/10.3390/genes13112075