ATRX loss refines the classification of anaplastic gliomas and identifies a subgroup of IDH mutant astrocytic tumors with better prognosis
Open accessAbstract
Mutation/loss of alpha-thalassemia/mental retardation syndrome X-linked (ATRX) expression has been described in anaplastic gliomas. The present study explored the role of ATRX status in the molecular classification of anaplastic gliomas and its impact on survival in the biomarker cohort of the NOA-04 anaplastic glioma trial. Patients (n = 133) of the NOA-04 trial were analyzed for ATRX expression using immunohistochemistry. ATRX status was correlated with age, histology, isocitrate dehydrogenase (IDH), 1p/19q, alternative lengthening of telomeres (ALT) and O6-methylguanine-DNA methyltransferase (MGMT) status, and the trial efficacy endpoints. Loss of ATRX expression was detected in 45 % of anaplastic astrocytomas (AA), 27 % of anaplastic oligoastrocytomas (AOA) and 10 % of anaplastic oligodendrogliomas (AO). It was mostly restricted to IDH mutant tumors and almost mutually exclusive with 1p/19q co-deletion. The ALT phenotype was significantly correlated with ATRX loss. ATRX and 1p/19q status were used to re-classify AOA: AOA harboring ATRX loss shared a similar clinical course with AA, whereas AOA carrying 1p/19q co-deletion shared a similar course with AO. Accordingly, in a Cox regression model including ATRX and 1p/19q status, histology was no longer significantly associated with time to treatment failure. Survival analysis showed a marked separation of IDH mutant astrocytic tumors into two groups based on ATRX status: tumors with ATRX loss had a significantly better prognosis (median time to treatment failure 55.6 vs. 31.8 months, p = 0.0168, log rank test). ATRX status helps better define the clinically and morphologically mixed group of AOA, since ATRX loss is a hallmark of astrocytic tumors. Furthermore, ATRX loss defines a subgroup of astrocytic tumors with a favorable prognosis.
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In adult HGG, ATRX loss associates with IDH mutations and TP53 loss and is associated with improved prognosis.
“Furthermore, in adult HGG, ATRX loss associates with IDH mutations and TP53 loss and is also associated with improved prognosis (Pekmezci et al., 2017; Wiestler et al., 2013), potentially due to better resection of focal tumors during surgery.”
From H3.3K27M Cooperates with Trp53 Loss and PDGFRA Gain in Mouse Embryonic Neural Progenitor Cells to Induce Invasive High-Grade Gliomas (2017) · cites this paper as Wiestler et al., 2013
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Cites
The 2007 WHO Classification of Tumours of the Central Nervous System
Louis, D. N., Ohgaki, H., Wiestler, O. D., Cavenee, W. K., Burger, P. C., Jouvet, A., Scheithauer, B. W., & Kleihues, P. (2007) · Acta Neuropathologica · doi:10.1007/s00401-007-0243-4 · Cited by 15,422 · see citing works
Comprehensive genomic characterization defines human glioblastoma genes and core pathways
The Cancer Genome Atlas Research Network (2008) · Nature · doi:10.1038/nature07385 · Cited by 7,735 · see citing works
Verhaak, R. G. W., Hoadley, K. A., Purdom, E., Wang, V., Qi, Y., Wilkerson, M. D., Miller, C. R., Ding, L., Golub, T., Mesirov, J. P., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2009.12.020 · Cited by 7,575 · see citing works
Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma
Schwartzentruber, J., Korshunov, A., Liu, X.-Y., Jones, D. T. W., Pfaff, E., Jacob, K., Sturm, D., Fontebasso, A. M., Quang, D.-A. K., Tönjes, M., et al. (2012) · Nature · doi:10.1038/nature10833 · Cited by 2,631 · see citing works
Self-citationIdentification of a CpG Island Methylator Phenotype that Defines a Distinct Subgroup of Glioma
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. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.03.017 · Cited by 2,337 · see citing works
IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype
Turcan, S., Rohle, D., Goenka, A., Walsh, L. A., Fang, F., Yilmaz, E., Campos, C., Fabius, A. W. M., Lu, C., Ward, P. S., et al. (2012) · Nature · doi:10.1038/nature10866 · Cited by 1,974 · see citing works
Sturm, D., Witt, H., Hovestadt, V., Khuong-Quang, D.-A., Jones, D. T. W., Konermann, C., Pfaff, E., Tönjes, M., Sill, M., Bender, S., et al. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.08.024 · Cited by 1,828 · see citing works
Self-citationKillela, P. J., Reitman, Z. J., Jiao, Y., Bettegowda, C., Agrawal, N., Diaz, L. A., Friedman, A. H., Friedman, H., Gallia, G. L., Giovanella, B. C., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1303607110 · Cited by 1,368 · see citing works
van den Bent, M. J., Brandes, A. A., TAPHOORN, M. J. B., Kros, J. M., Kouwenhoven, M. C. M., Delattre, J., Bernsen, H. J. J. A., Frénay, M., Tijssen, C. C., Grisold, W., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2012.43.2229 · Cited by 1,220 · see citing works
Cairncross, G. J., Wang, M., Shaw, E., Jenkins, R. B., Brachman, D. G., Buckner, J. C., Fink, K., Souhami, L., Laperrière, N., Curran, W., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2012.43.2674 · Cited by 1,152 · see citing works
Altered Telomeres in Tumors with <i>ATRX</i> and <i>DAXX</i> Mutations
Heaphy, C. M., de Wilde, R. F., Jiao, Y., Klein, A. P., Edil, B. H., Shi, C., Bettegowda, C., Rodriguez, F. J., Eberhart, C. G., Hebbar, S., et al. (2011) · Science · doi:10.1126/science.1207313 · Cited by 1,083 · see citing works
Khuong-Quang, D.-A., Buczkowicz, P., Rakopoulos, P., Liu, X.-Y., Fontebasso, A. M., Bouffet, E., Bartels, U., Albrecht, S., Schwartzentruber, J., Letourneau, L., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-012-0998-0 · Cited by 1,028 · see citing works
Self-citationHartmann, C. J., Hentschel, B., Wick, W., Capper, D., Felsberg, J., Simon, M., Westphal, M., Schackert, G., Meyermann, R., Pietsch, T., et al. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0781-z · Cited by 823 · see citing works
Self-citationWick, W., Hartmann, C. J., Engel, C., Stoffels, M., Felsberg, J., Stockhammer, F., Sabel, M., Koeppen, S., Ketter, R., Meyermann, R., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.23.6497 · Cited by 803 · see citing works
Self-citationSmith, J. S., Perry, A., Borell, T. J., Lee, H. K., O'Fallon, J. R., Hosek, S. M., Kimmel, D. W., Yates, A. J., Burger, P. C., Scheithauer, B. W., et al. (2000) · Journal of Clinical Oncology · doi:10.1200/jco.2000.18.3.636 · Cited by 803 · see citing works
van den Bent, M. J., Carpentier, A. F., Brandes, A. A., Sanson, M., TAPHOORN, M. J. B., Bernsen, H. J. J. A., Frénay, M., Tijssen, C. C., Grisold, W., Sipos, L., et al. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2005.04.6078 · Cited by 745 · see citing works
Frequent ATRX , CIC , FUBP1 and IDH1 mutations refine the classification of malignant gliomas
Jiao, Y., Killela, P. J., Reitman, Z. J., Rasheed, B. A., Heaphy, C. M., de Wilde, R. F., Rodríguez, F. J., Rosemberg, S., Oba‐Shinjo, S. M., Marie, S. K. N., et al. (2012) · Oncotarget · doi:10.18632/oncotarget.588 · Cited by 584 · see citing works
Lai, A., Kharbanda, S., Pope, W. B., Tran, A. N., Solis, O. E., Peale, F. V., Jr., Forrest, W. F., Pujara, K., Carrillo, J., Pandita, A., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.33.8715 · Cited by 432 · see citing works
Liu, X.-Y., Gerges, N., Korshunov, A., Sabha, N., Khuong-Quang, D.-A., Fontebasso, A. M., Fleming, A. J., Hadjadj, D., Schwartzentruber, J., Majewski, J., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-012-1031-3 · Cited by 428 · see citing works
Self-citationWhole exome sequencing identifies ATRX mutation as a key molecular determinant in lower-grade glioma
Kannan, K. S., Inagaki, A., Silber, J., Gorovets, D. J., Zhang, J., Kastenhuber, E. R., Heguy, A., Petrini, J. H. J., Chan, T. A.-T., & Huse, J. T. (2012) · Oncotarget · doi:10.18632/oncotarget.689 · Cited by 277 · see citing works
Molecular Genetic Evidence for Subtypes of Oligoastrocytomas
Maintz, D. C., FIEDLER, K., Koopmann, J., Rollbrocker, B., NECHEV, S., Lenartz, D., Stangl, A. P., Louis, D. N., Schramm, J., Wiestler, O. D., et al. (1997) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199710000-00003 · Cited by 246 · see citing works
Weller, M., Stupp, R., Hegi, M. E., van den Bent, M. J., Tonn, J. C., Sanson, M., Wick, W., & Reifenberger, G. (2012) · Neuro-Oncology · doi:10.1093/neuonc/nos206 · Cited by 203 · see citing works
Self-citationMiller, C. R., Dunham, C. P., Scheithauer, B. W., & Perry, A. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2006.08.1497 · Cited by 178 · see citing works
Kros, J. M., Gorlia, T., Kouwenhoven, M. C. M., Zheng, P., Collins, V. P., Figarella-Branger, D. F., Giangaspero, F., Giannini, C., Mokhtari, K., Mørk, S. J., et al. (2007) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/01.jnen.0000263869.84188.72 · Cited by 156 · see citing works
Lacayo, N. J., Meshinchi, S., Kinnunen, P., Yu, R., Wang, Y. C., Stuber, C. M., Douglas, L., Wahab, R., Becton, D. L., Weinstein, H. J., et al. (2004) · Blood · doi:10.1182/blood-2003-12-4449 · Cited by 118 · see citing works
The Chromatin Remodelling Factor dATRX Is Involved in Heterochromatin Formation
Bassett, A. R., Cooper, S., Ragab, A., & TRAVERS, A. A. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002099 · Cited by 36 · see citing works
Weisbrod, A. B., Zhang, L., Jain, M., et al. (2013) · Hormones and Cancer · doi:10.1007/s12672-013-0134-1 · Cited by 33 · see citing works
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Suzuki, H., Aoki, K., Chiba, K., Sato, Y., Shiozawa, Y., Shiraishi, Y., Shimamura, T., Niida, A., Motomura, K., Ohka, F., et al. (2015) · Nature Genetics · doi:10.1038/ng.3273 · Cited by 831 · see citing works
Olar, A., Wani, K. M., Alfaro-Munoz, K. D., Heathcock, L. E., van Thuijl, H. F., Gilbert, M. R., Armstrong, T. S., Sulman, E. P., Cahill, D. P., Vera-Bolanos, E., et al. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1398-z · Cited by 354 · see citing works
Pekmezci, M., Rice, T., Molinaro, A. M., Walsh, K. M., Decker, P. A., Hansen, H., Sicotte, H., Kollmeyer, T. M., McCoy, L. S., Sarkar, G., et al. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1690-1 · Cited by 319 · see citing works
Pathania, M., De Jay, N., Maestro, N., Harutyunyan, A. S., Nitarska, J., Pahlavan, P., Henderson, S., Mikael, L. G., Richard-Londt, A., Zhang, Y., et al. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.09.014 · Cited by 264 · see citing works
Wang, Y., Yang, J., Wild, A. T., Wu, W. H., Shah, R., Danussi, C., Riggins, G. J., Kannan, K., Sulman, E. P., Chan, T. A., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-08905-8 · Cited by 184 · see citing works
Dubbink, H. J., Atmodimedjo, P. N., Kros, J. M., French, P. J., Sanson, M., Idbaih, A., Wesseling, P., Enting, R., Spliet, W., Tijssen, C., et al. (2016) · Neuro-Oncology · doi:10.1093/neuonc/nov182 · Cited by 163 · see citing works
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Nasrallah, M. P., Zhao, J., Tsai, C. C., Meredith, D., Marostica, E., Ligon, K. L., Golden, J. A., & Yu, K.-H. (2023) · Med · doi:10.1016/j.medj.2023.06.002 · Cited by 67 · see citing works
- Authors
- Wiestler, B., Capper, D., Holland-Letz, T., Korshunov, A., von Deimling, A., Pfister, S. M., Platten, M., Weller, M., & Wick, W.
- Affiliations
- German Cancer Research Center (DE)
- University Hospital Zurich (CH)
- Corresponding author
- Wick, Wolfgang
- ORCID
- Venue
- Acta Neuropathologica
- Published
- 2013-08-01
- Volume
- 126
- Issue
- 3
- Pages
- 443-451
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- OpenAlex
- W2158501128
- Cited by
- 346
- References
- 27
- Citations by year
- 2026: 6 · 2025: 18 · 2024: 14 · 2023: 21 · 2022: 25 · 2021: 25 · 2020: 30 · 2019: 25 · 2018: 36 · 2017: 31 · 2016: 40 · 2015: 45 · 2014: 27 · 2013: 3
- FWCI
- 18.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Bundesministerium für Bildung und Forschung
- Nationales Centrum für Tumorerkrankungen Heidelberg
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- ATRX loss, anaplastic glioma, anaplastic astrocytoma, anaplastic oligoastrocytoma, anaplastic oligodendroglioma, IDH mutation, 1p/19q codeletion, alternative lengthening of telomeres, MGMT promoter status, molecular classification, prognosis, time to treatment failure
- MeSH terms
- X-linked Nuclear Protein, Adult, Aged, Brain Neoplasms, Chromosome Deletion, DNA Helicases, Glioma, Humans, Isocitrate Dehydrogenase, Middle Aged, Mutation, Nuclear Proteins, Prognosis, Genetic Predisposition to Disease, Tumor Suppressor Proteins
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