Methylation arrays

The CNVs were analyzed with Illumina methylation arrays using the conumee Bioconductor package in R using default settings. DNA copy-number segmentations were retrieved from uploading raw IDAT files to www.molecularneuropathology.org. Segmentation files were then imported to IGV (version 2.4.14) for visualization and identification of CNVs. Focal copy-number alterations were defined as regions that span a small proportion (≤25%) of the chromosome arm, whereas other regions were defined as broad alterations. Mean segment value of −0.2 and 0.2 were used as thresholds for losses and gains, respectively. Copy-number plots were manually examined for selected copy-number alterations. When copy-number information was also available from sequencing data, both results were compared and adjudicated. Adjudicated results are shown in Fig. 4 for selected recurrent somatic alterations. q values for focal, broad copy-number alterations were determined using GISTIC (v2.0.23). GISTIC analysis was performed with the following parameters: 0.9 confidence level, 0.2 amplification and deletion thresholds, 0.25 focal length cutoff, and the gene GISTIC algorithm was flagged. The broad analysis and arm peel advanced parameters were also flagged.