Media type: E-Article Title: IDH1 mutations in grade II astrocytomas are associated with unfavorable progression‐free survival and prolonged postrecurrence survival Contributor: Thon, Niklas; Eigenbrod, Sabina; Kreth, Simone; Lutz, Juergen; Tonn, Joerg‐Christian; Kretzschmar, Hans; Peraud, Aurelia; Kreth, Friedrich‐Wilhelm imprint: Wiley, 2012 Published in: Cancer Language: English DOI: 10.1002/cncr.26298 ISSN: 0008-543X; 1097-0142 Keywords: Cancer Research ; Oncology Origination: Footnote: Description: <jats:title>Abstract</jats:title><jats:sec><jats:title>BACKGROUND:</jats:title><jats:p>The favorable prognostic impact of mutations in the <jats:italic>IDH1</jats:italic> gene is well documented for malignant gliomas; its influence on World Health Organization (WHO) grade II astrocytomas, however, is still under debate.</jats:p></jats:sec><jats:sec><jats:title>METHODS:</jats:title><jats:p>A previously published database of 127 predominantly surgically treated patients harboring WHO grade II astrocytomas was revisited. Patients were screened for <jats:italic>TP53</jats:italic> mutations (sequencing analysis)<jats:italic>, IDH1</jats:italic> mutations (pyrosequencing), and <jats:italic>MGMT</jats:italic> promoter methylation (methylation‐specific polymerase chain reaction and bisulfite sequencing). Endpoints were overall survival, progression‐free survival (PFS), time to malignant transformation, and postrecurrence survival. Radiotherapy was usually withheld until tumor progression/malignant transformation occurred.</jats:p></jats:sec><jats:sec><jats:title>RESULTS:</jats:title><jats:p><jats:italic>IDH1</jats:italic> mutations, <jats:italic>TP53</jats:italic> mutations, and methylated <jats:italic>MGMT</jats:italic> promoters were seen in 78.1%, 51.2%, and 80.0% of the analyzed tumors, respectively. <jats:italic>IDH1</jats:italic> mutations, which were significantly associated with <jats:italic>TP53</jats:italic> mutations and/or <jats:italic>MGMT</jats:italic> promoter methylation (<jats:italic>P</jats:italic> < .001), resulted in shortened PFS (median, 47 vs 84 months; <jats:italic>P</jats:italic> = .004); postrecurrence survival, however, was significantly increased in those patients undergoing malignant transformation (median, 49 vs 13.5 months; <jats:italic>P</jats:italic> = .006). Overall survival was not affected by <jats:italic>IDH1</jats:italic>. A similar pattern of influence was seen for <jats:italic>MGMT</jats:italic> promoter methylation. Methylated tumors did significantly worse (better) in terms of PFS (postrecurrence survival); a low number of unmethylated tumors, however, limited the power of this analysis. Conversely, <jats:italic>TP53</jats:italic> mutations were stringently associated with a worse prognosis throughout the course of the disease.</jats:p></jats:sec><jats:sec><jats:title>CONCLUSIONS:</jats:title><jats:p><jats:italic>IDH1</jats:italic> mutations are associated with a Janus headlike phenomenon; unfavorable prognostic influence on PFS turns into favorable impact on postrecurrence survival. A similar pattern of influence might exist for <jats:italic>MGMT</jats:italic> methylation. Cancer 2011;. © 2011 American Cancer Society.</jats:p></jats:sec> Access State: Open Access