IDH mutations predict shorter survival in chondrosarcoma

Background. Recent studies have shown that isocitrate dehydrogenase 1/2 (IDH1/2) activating mutations occur in a variety of cancers, including acute myeloid leukemia (AML), gliomas, and chondrosarcomas (CHSs). In CHS no effect of IDH mutation on overall survival (OS) has been reported. The aim of our study was to assess the prevalence of known cancer-related genes mutations in CHSs, as well as their prognostic role on patients' survival.Methods. We included 80 patients (F:M- 1:1.3; mean age: 58 years; range 27-86) with histologically confirmed CHS (G1:29; G2:34; G3:17) treated at Cancer Center-Institute between 1996 and 2013. DNA from FFPE samples was subjected to library preparation with the Ion AmpliSeq Cancer Hotspot Panel v2 and sequenced on PGM Ion Torrent. The following clinical factors were analyzed: tumor localization, histological subtype and grade, type of surgery, presence of metastases, age and sex. Statistical analysis of impact of IDH1/2 mutation on OS was performed with log-rank test with significance level of 5%.Results. Among clinical features only the histological grade influenced OS. Through deep sequencing 1784 single nucleotide variants (SNVs) with quality 20 or higher were identified in 50 genes. Of them, 426 were considered as pathogenic or likely pathogenic. Activating IDH mutations were found in 27 patients (33.75%) including 17 R132 IDH1 (21.25%), 10 R172 IDH2 (12.5%) and 3 R140 IDH2 variants (3.75%). Three patients had concurrent mutation in IDH1 and 2. The R140 IDH2 mutant has not been reported to date in chondrosarcoma patient. The OS for CHS patients with IDH mutations was significantly lower than those without mutation (p=0.001). No other genetic feature had impact on OS.Conclusions. In CHS, tumor histology and IDH-mutation status are important predictors for prolonged OS. The R140 IDH2 may also be the novel target for treatment of CHS patients.