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| Status |
Public on Aug 26, 2013 |
| Title |
MGMT-STP27 methylation status as Predictive Marker for Response to PCV in Anaplastic Oligodendrogliomas and Oligoastrocytomas. A report from EORTC study 26951 [27K] |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by array
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| Summary |
Purpose: The long-term follow-up results from the EORTC-26951 trial showed that the addition of PCV after radiotherapy increases survival in anaplastic oligodendrogliomas/oligoastrocytomas (AOD/AOA). However, some patients appeared to benefit more from PCV treatment than others.
Experimental Design: We performed genome-wide methylation profiling of 115 samples included in the EORTC-26951 trial and extracted the CpG island hypermethylated phenotype (CIMP) and MGMT promoter methylation (MGMT-STP27) status.
Results: We first demonstrate that methylation profiling can be performed on archival tissues with a performance that is similar to snap frozen tissue samples. We then performed methylation profiling on EORTC-26951 clinical trial samples. Univariate analysis indicated that CIMP+ or MGMT-STP27 methylated tumors had an improved survival compared to CIMP- and/or MGMT-STP27 unmethylated tumors (median overall survival (OS) 1.05 v. 6.46 years and 1.06 v. 3.8 years, both P<0.0001 for CIMP and MGMT-STP27 status respectively). Multivariable analysis indicates that CIMP and MGMT-STP27 are significant prognostic factors for survival in presence of age, sex performance score and review diagnosis in the model.Multivariate analysis indicates that CIMP and MGMT-STP27 status are prognostic factors for survival independent of age, sex, performance score and review diagnosis. CIMP+ and MGMT-STP27 methylated tumors showed a clear benefit from adjuvant PCV chemotherapy: the median OS of CIMP+ samples in the RT and RT-PCV arms was 3.27 and 9.51 years respectively P=0.0033; for MGMT-STP27 methylated samples it was 1.98 and 8.65 years. There was no such benefit for CIMP- or for MGMT-STP27 unmethylated tumors. MGMT-STP27 status remained significant in an interaction test (P=0.003). Statistical analysis of microarray (SAM) identified 259 novel CpGs associated with treatment response.
Conclusions: MGMT-STP27 may be used to guide treatment decisions in this tumor type.
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| Overall design |
Bisulphite converted DNA from the 58 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip
The following sample characteristics are provided;
OS: overall survival; PFS: progression free survival; CIMP: CpG Island Methylator phenotype; IGS: Intrinsic Glioma subtype; MGMT: O6-methylguanine-DNA-methyltransferase; OR diagn: original diagnosis; Rev diag: review diagnosis; Tum loc: Tumor location; Perf: Performance score; TRT: treatment
Performance is based on the ECOG performance status
Tum loc: tumor location indicated by 1: Biopsy; 2: Partial Resection; 3: Total Resection.
The MGMT promoter methylation status was determined previously (van den Bent et al, J. Clin Oncol 27: 5881-6, 2009) using MS-MLPA and may differ from the MGMT-SPT27 status.
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| Contributor(s) |
van den Bent MJ, Erdem-Eraslan L, Idbaih A, de Rooi J, Eilers PH, Spliet WG, den Dunnen WF, Tijssen C, Wesseling P, Sillevis Smitt PA, Kros JM, Gorlia T, French PJ |
| Citation(s) |
23948976 |
| Submission date |
Jul 01, 2013 |
| Last update date |
Jan 02, 2015 |
| Contact name |
Pim French |
| E-mail(s) |
p.french@erasmusmc.nl
|
| Phone |
+31 10 70443 33
|
| Organization name |
Erasmus MC
|
| Department |
Neurology
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| Lab |
Neurooncology
|
| Street address |
Dr Molewaterplein 50
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| City |
Rotterdam |
| ZIP/Postal code |
2040CA |
| Country |
Netherlands |
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| Platforms (1) |
| GPL8490 |
Illumina HumanMethylation27 BeadChip (HumanMethylation27_270596_v.1.2) |
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| Samples (58)
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| This SubSeries is part of SuperSeries: |
| GSE48462 |
MGMT-STP27 methylation status as Predictive Marker for Response to PCV in Anaplastic Oligodendrogliomas and Oligoastrocytomas. A report from EORTC study 26951 |
|
| Relations |
| BioProject |
PRJNA210233 |
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