%0 Journal Article %1 vandenBent:2013:Clin-Cancer-Res:23948976 %A van den Bent, M J %A Erdem-Eraslan, L %A Idbaih, A %A de Rooi, J %A Eilers, P H %A Spliet, W G %A den Dunnen, W F %A Tijssen, C %A Wesseling, P %A Sillevis Smitt, P A %A Kros, J M %A Gorlia, T %A French, P J %D 2013 %J Clin Cancer Res %K CIMP MGMT cancer-research fulltext methylation shouldread survival therapeutic-impact therapy %N 19 %P 5513-5522 %R 10.1158/1078-0432.CCR-13-1157 %T MGMT-STP27 methylation status as predictive marker for response to PCV in anaplastic Oligodendrogliomas and Oligoastrocytomas. A report from EORTC study 26951 %U https://www.ncbi.nlm.nih.gov/pubmed/23948976 %V 19 %X The long-term follow-up results from the EORTC-26951 trial showed that the addition of procarbazine, CCNU, and vincristine (PCV) after radiotherapy increases survival in anaplastic oligodendrogliomas/oligoastrocytomas (AOD/AOA). However, some patients appeared to benefit more from PCV treatment than others.We conducted 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.We first show that methylation profiling can be conducted on archival tissues with a performance that is similar to snap-frozen tissue samples. We then conducted methylation profiling on EORTC-26951 clinical trial samples. Univariate analysis indicated that CIMP+ or MGMT-STP27 methylated tumors had an improved survival compared with CIMP- and/or MGMT-STP27 unmethylated tumors median overall survival (OS), 1.05 vs. 6.46 years and 1.06 vs. 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. 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.MGMT-STP27 may be used to guide treatment decisions in this tumor type.

@article{vandenBent:2013:Clin-Cancer-Res:23948976, abstract = {The long-term follow-up results from the EORTC-26951 trial showed that the addition of procarbazine, CCNU, and vincristine (PCV) after radiotherapy increases survival in anaplastic oligodendrogliomas/oligoastrocytomas (AOD/AOA). However, some patients appeared to benefit more from PCV treatment than others.We conducted 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.We first show that methylation profiling can be conducted on archival tissues with a performance that is similar to snap-frozen tissue samples. We then conducted methylation profiling on EORTC-26951 clinical trial samples. Univariate analysis indicated that CIMP+ or MGMT-STP27 methylated tumors had an improved survival compared with CIMP- and/or MGMT-STP27 unmethylated tumors [median overall survival (OS), 1.05 vs. 6.46 years and 1.06 vs. 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. 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.MGMT-STP27 may be used to guide treatment decisions in this tumor type.}, added-at = {2018-12-21T01:22:36.000+0100}, author = {van den Bent, M J and Erdem-Eraslan, L and Idbaih, A and de Rooi, J and Eilers, P H and Spliet, W G and den Dunnen, W F and Tijssen, C and Wesseling, P and Sillevis Smitt, P A and Kros, J M and Gorlia, T and French, P J}, biburl = {https://www.bibsonomy.org/bibtex/2f9fcfcac4f3f31490284e37d2fcd3321/marcsaric}, description = {MGMT-STP27 methylation status as predictive marker for response to PCV in anaplastic Oligodendrogliomas and Oligoastrocytomas. A report from EORTC ... - PubMed - NCBI}, doi = {10.1158/1078-0432.CCR-13-1157}, interhash = {1371e56e122d2110740d9b2e91a4046b}, intrahash = {f9fcfcac4f3f31490284e37d2fcd3321}, journal = {Clin Cancer Res}, keywords = {CIMP MGMT cancer-research fulltext methylation shouldread survival therapeutic-impact therapy}, month = oct, number = 19, pages = {5513-5522}, pmid = {23948976}, timestamp = {2018-12-21T01:22:55.000+0100}, title = {MGMT-STP27 methylation status as predictive marker for response to PCV in anaplastic Oligodendrogliomas and Oligoastrocytomas. A report from EORTC study 26951}, url = {https://www.ncbi.nlm.nih.gov/pubmed/23948976}, volume = 19, year = 2013 }