IDH1 mutations in low-grade astrocytomas predict survival but not response to temozolomide
Abstract
Background: Mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) have been implicated in tumorigenesis of gliomas. Patients with high-grade astrocytomas with IDH1 or IDH2 mutations were reported to have a better survival, but it is unknown if this improved survival also holds for low-grade astrocytoma and whether these mutations predict outcome to specific treatment.
Methods: We retrospectively investigated the correlation of IDH1 and IDH2 mutations with overall survival and response to temozolomide in a cohort of patients with dedifferentiated low-grade astrocytomas treated with temozolomide at the time of progression after radiotherapy.
Results: IDH1 mutations were present in 86% of the 49 progressive astrocytomas. No mutations in IDH2 were found. Presence of IDH1 mutations were early events and significantly improved overall survival (median survival 48 vs 98 months), but did not affect outcome of temozolomide treatment.
Conclusion: These results indicate that IDH1 mutations identify a subgroup of gliomas with an improved survival, but are unrelated to the temozolomide response.
Get full access to this article
View all available purchase options and get full access to this article.
REFERENCES
1.
Balss J, Meyer J, Mueller W, Korshunov A, Hartmann C, von Deimling A. Analysis of the IDH1 codon 132 mutation in brain tumors. Acta Neuropathol 2008;116:597–602.
2.
Bleeker FE, Lamba S, Leenstra S, et al. IDH1 mutations at residue p.R132 (IDH1(R132)) occur frequently in high-grade gliomas but not in other solid tumors. Hum Mutat 2009;30:7–11.
3.
Parsons DW, Jones S, Zhang X, et al. An integrated genomic analysis of human glioblastoma multiforme. Science 2008;321:1807–1812.
4.
Watanabe T, Nobusawa S, Kleihues P, Ohgaki H. IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. Am J Pathol (in press 2009).
5.
Yan H, Parsons DW, Jin G, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med 2009;360:765–773.
6.
Macdonald DR, Cascino TL, Schold SC, Jr., Cairncross JG. Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 1990;8:1277–1280.
7.
van der Sijp JR, van Meerbeeck JP, Maat AP, et al. Determination of the molecular relationship between multiple tumors within one patient is of clinical importance. J Clin Oncol 2002;20:1105–1114.
8.
Kouwenhoven MC, Kros JM, French PJ, et al. 1p/19q loss within oligodendroglioma is predictive for response to first line temozolomide but not to salvage treatment. Eur J Cancer 2006;42:2499–2503.
Information & Authors
Information
Published In
Copyright
© 2009.
Publication History
Published online: November 23, 2009
Published in print: November 24, 2009
Authors
Metrics & Citations
Metrics
Citation information is sourced from Crossref Cited-by service.
Citations
Download Citations
If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.
Cited By
- Delivery of PARP inhibitors through 2HG-incorporated liposomes for synergistically targeting DNA repair in cancer, Cancer Letters, 604, (217268), (2024).https://doi.org/10.1016/j.canlet.2024.217268
- Noncanonical (Non-R132H) IDH-Mutated Gliomas, Glioblastoma - Current Evidence, (2023).https://doi.org/10.5772/intechopen.105469
- Temozolomide, Procarbazine and Nitrosoureas in the Therapy of Malignant Gliomas: Update of Mechanisms, Drug Resistance and Therapeutic Implications, Journal of Clinical Medicine, 12, 23, (7442), (2023).https://doi.org/10.3390/jcm12237442
- Evaluation of the effectiveness of multicomponent treatment in the progression of primary low-grade brain gliomas. Own experience, Russian Journal of Oncology, 27, 4, (157-163), (2023).https://doi.org/10.17816/onco456888
- Radiomics and Radiogenomics in Glioma, Functional Neuroradiology, (1313-1321), (2023).https://doi.org/10.1007/978-3-031-10909-6_55
- Ten-year survival in glioblastoma patient with neurofibromatosis type 1: illustrative case, Journal of Neurosurgery: Case Lessons, 3, 4, (2022).https://doi.org/10.3171/CASE21630
- Risk factors for the development of an early recurrence of gemistocytic astrocytomas and their clinical significance, Russian Journal for Personalized Medicine, 2, 4, (14-22), (2022).https://doi.org/10.18705/2782-3806-2022-2-4-14-22
- Clinical development of IDH1 inhibitors for cancer therapy, Cancer Treatment Reviews, 103, (102334), (2022).https://doi.org/10.1016/j.ctrv.2021.102334
- 5-ALA Fluorescence Is a Powerful Prognostic Marker during Surgery of Low-Grade Gliomas (WHO Grade II)—Experience at Two Specialized Centers, Cancers, 13, 11, (2540), (2021).https://doi.org/10.3390/cancers13112540
- Opposed Interplay between IDH1 Mutations and the WNT/β-Catenin Pathway: Added Information for Glioma Classification, Biomedicines, 9, 6, (619), (2021).https://doi.org/10.3390/biomedicines9060619
- See more
Loading...
View Options
Login options
Check if you have access through your login credentials or your institution to get full access on this article.
Personal login Institutional LoginPurchase Options
The neurology.org payment platform is currently offline. Our technical team is working as quickly as possible to restore service.
If you need immediate support or to place an order, please call or email customer service:
- 1-800-638-3030 for U.S. customers - 8:30 - 7 pm ET (M-F)
- 1-301-223-2300 for customers outside the U.S. - 8:30 - 7 pm ET (M-F)
- [email protected]
We appreciate your patience during this time and apologize for any inconvenience.